Compositions and Related Methods for Fungal Control

Abstract

The present disclosure provides conidial germination inhibitor (CGI) factors, CGI factor precursors, CGI factor fragments, and CGI factor motifs, and compositions comprising CGI factors, CGI factor precursors, CGI factor fragments, and CGI factor motifs. The present disclosure also provides recombinant DNA constructs and vectors encoding CGI factors, CGI factor precursors, CGI factor fragments, and CGI factor motifs, and transgenic organisms comprising recombinant DNA constructs or vectors encoding CGI factors, CGI factor precursors, CGI factor fragments, and CGI factor motifs. In addition, the present disclosure provides methods of controlling or inhibiting fungal growth and infection, and methods of treating fungal diseases using CGI factors, CGI factor precursors, CGI factor fragments, and CGI factor motifs.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 63 / 225,356, filed July 23, 2021, which is incorporated herein by reference in its entirety.

[0002] Electronic Sequence Listing Reference The contents of the electronic sequence listing (237212000140SEQLIST.xml; size: 5,682,035 bytes; and creation date: July 15, 2022) are incorporated herein by reference in their entirety.

[0003] Field of the Disclosure The present disclosure relates to antifungal or fungicide agents, compositions and organisms comprising the antifungal or fungicide agents, and methods of using the antifungal or fungicide agents to inhibit or control fungi, such as fungal pathogens. [Background technology]

[0004] Background of the Disclosure The kingdom Fungi encompasses a diverse group of organisms, some of which can act as pathogens on various hosts. Pathogenic fungi have adverse effects on both human and animal health, either by direct infection or by indirect effects from secreted toxins. Food spoilage and crop losses due to uncontrolled fungal pathogens of one or more plant products can also result in significant agricultural and economic losses. Thus, there is a need for agents that can control or inhibit the growth of fungal pathogens, as well as compositions that contain agents that can control or inhibit fungal growth and can be used to treat fungal infections in biological systems. Summary of the Invention [Means for solving the problem]

[0005] Summary of the Disclosure In one aspect of the disclosure, provided herein is a method for reducing fungal growth or reproduction, comprising administering to the fungus an effective amount of at least one conidial germination inhibitor (CGI) factor, CGI factor precursor, CGI factor fragment, or CGI factor motif, wherein the CGI factor comprises an amino acid sequence having at least 80% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 961-1920, SEQ ID NOs: 1957-2189, SEQ ID NOs: 2194-2210, SEQ ID NOs: 2215-2243, SEQ ID NOs: 2457-3361, and SEQ ID NOs: 5707-5731, or the CGI factor motif comprises an amino acid sequence having at least 80% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 1921-1956. and optionally an agriculturally or pharma- ceutically acceptable carrier, thereby reducing fungal growth or reproduction compared to a control fungus to which the antifungal composition has not been provided. The method of claim 1, further comprising providing an antifungal composition comprising a CGI factor, a CGI factor precursor, a CGI factor fragment, or a CGI factor motif, and optionally an agriculturally or pharma-ceutically acceptable carrier, where the amino acid sequence of the CGI factor is not an amino acid sequence of an alpha pheromone naturally expressed by the fungus, or where a nucleotide sequence encoding the at least one CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is not present in the genome of the fungus, thereby reducing fungal growth or reproduction compared to a control fungus to which the antifungal composition has not been provided.

[0006] In another aspect of the present disclosure, provided herein is a recombinant DNA construct comprising a heterologous promoter operably linked to a nucleic acid molecule comprising a nucleotide sequence encoding a conidial germination inhibitor (CGI) factor, a CGI factor precursor, or a CGI factor fragment, wherein the nucleotide sequence (a) encodes at least one CGI factor comprising an amino acid sequence having at least 80% sequence identity to at least one of SEQ ID NOs: 961-1920, 1957-2189, 2194-2210, 2215-2243, 2457-3361, and 5707-5731, or (b) encodes at least one CGI factor motif comprising at least one of SEQ ID NOs: 1921-1956, wherein the nucleotide sequence optionally has codons optimized for heterologous expression. Related embodiments include cells or organisms, such as transgenic plants or plant parts (eg, rootstocks or scions) in which such recombinant DNA constructs are heterologously expressed.

[0007] In another aspect of the disclosure, provided herein is a method for preventing or reducing a disease caused by a fungal pathogen in a plant, comprising administering to a plant an effective amount of at least one conidial germination inhibitor (CGI) factor, CGI factor precursor, CGI factor fragment, or CGI factor motif, wherein the CGI factor comprises an amino acid sequence having at least 80% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 961-1920, SEQ ID NOs: 1957-2189, SEQ ID NOs: 2194-2210, SEQ ID NOs: 2215-2243, SEQ ID NOs: 2457-3361, and SEQ ID NOs: 5707-5731, or the CGI factor motif comprises an amino acid sequence having at least 80% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 1921-1956. and optionally an agriculturally acceptable carrier, whereby disease caused by the fungal pathogen is prevented or reduced in a plant compared to a control plant to which the antifungal composition is not provided, wherein the amino acid sequence of the CGI factor is not the amino acid sequence of an alpha pheromone naturally expressed by a fungal pathogen or the nucleotide sequence encoding the at least one CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is not present in the genome of the fungal pathogen, thereby providing an antifungal composition comprising a CGI factor, a CGI factor precursor, a CGI factor fragment, or a CGI factor motif, and optionally an agriculturally acceptable carrier, whereby disease caused by the fungal pathogen is prevented or reduced in a plant compared to a control plant to which the antifungal composition is not provided.

[0008] Other aspects of the present disclosure relate to methods of preventing or treating fungal diseases in organisms such as plants and animals, e.g., non-human animals; methods of preventing or treating fungal infection or growth on surfaces, including non-biological surfaces; and compositions, such as substrates or matrices, that have antifungal properties, e.g., resistance to fungal contamination or growth. [Brief description of the drawings]

[0009] BRIEF DESCRIPTION OF THE DRAWINGS [Figure 1A]The experimental set-up for the conidial germination inhibition assay is shown. Bright field images showing the effect of control treatments on conidial germination at 40x (top row) and 400x (bottom row) magnification are shown. Untreated conidia (left panel) and conidia treated with 50% (w / v) ethanol (right panel) were used as negative controls, and 100 μM fenpiclonil (middle panel) was used as a positive control condition. Asterisks in the 400x images highlight germinating conidia. [Figure 1B] FIG. 1 illustrates the experimental setup for the conidial germination inhibition assay. FIG. 2 illustrates an exemplary 96-well plate layout for the conidial germination inhibition assay. As indicated (from left to right): Un, untreated; eth, 50% ethanol; fen, fenpiclocil; 6, peptide 106; 7, peptide 107; 12, peptide 112; 13, peptide 113; 14, peptide 114; and 15, peptide 115. [Figure 2A] Results of experiments testing inhibition of germination of Fusarium and Botrytis by candidate CGI factors are shown. Resazurin fluorescence is displayed for Fusarium conidia (top panels) or Botrytis conidia (bottom panels) incubated with gradient concentrations (scaled on the left) of candidate CGI factors or controls. In Figures 2A-2E, Pep106, peptide 106; Pep107, peptide 107; Pep112, peptide 112; Pep113, peptide 113; Pep114, peptide 114, untreated and 50% EtOH treatment were used as negative control conditions, and fenpiclonil was used as a positive control condition. [Figure 2B]2A-2E show the results of an experiment testing inhibition of germination of Fusarium and Botrytis by candidate CGI factors. Fluorescence quantification of resazurin for Fusarium conidia incubated with 10 μM, 100 μM, 375 μM, and 1 mM candidate CGI factors or controls (scaled on the x-axis). In FIG. 2A-2E, Pep106, peptide 106; Pep107, peptide 107; Pep112, peptide 112; Pep113, peptide 113; Pep114, peptide 114, untreated and 50% EtOH treatment were used as negative control conditions, and fenpiclonil was used as a positive control condition. [Figure 2C] Figure 2 shows the results of an experiment testing inhibition of germination of Fusarium and Botrytis by candidate CGI factors. Resazurin fluorescence is shown for Botrytis conidia incubated with 10 μM, 100 μM, 375 μM, and 1 mM candidate CGI factors or controls (scaled on the x-axis). Pipetting errors occurred during the treatment of the 375 μM untreated and 50% ethanol conditions shown in Figures 2C and 2E. In Figures 2A-2E, Pep106, peptide 106; Pep107, peptide 107; Pep112, peptide 112; Pep113, peptide 113; Pep114, peptide 114, untreated and 50% EtOH treatment were used as negative control conditions, and fenpiclonil was used as a positive control condition. [Figure 2D] 2A-2E show the results of an experiment testing inhibition of germination of Fusarium and Botrytis by candidate CGI factors. Resazurin fluorescence is shown for Fusarium conidia incubated with 100 μM or 375 μM of candidate CGI factors or controls (scaled on the x-axis). In FIG. 2A-2E, Pep106, peptide 106; Pep107, peptide 107; Pep112, peptide 112; Pep113, peptide 113; Pep114, peptide 114, untreated and 50% EtOH treatment were used as negative control conditions, and fenpiclonil was used as a positive control condition. [Figure 2E]Figure 2 shows the results of an experiment testing inhibition of germination of Fusarium and Botrytis by candidate CGI factors. Resazurin fluorescence is shown for Botrytis conidia incubated with 100 μM or 375 μM candidate CGI factors or control (scaled on the x-axis). Pipetting errors occurred during the treatment of the 375 μM untreated and 50% ethanol conditions shown in Figures 2C and 2E. In Figures 2A-2E, Pep106, peptide 106; Pep107, peptide 107; Pep112, peptide 112; Pep113, peptide 113; Pep114, peptide 114, untreated and 50% EtOH treatment were used as negative control conditions, and fenpiclonil was used as a positive control condition. [Diagram 3] Fluorescence quantification of resazurin for Fusarium and Botrytis conidia incubated with 100 μM selected candidate CGI agents and controls. Three replicates of each fungal species were evaluated for each condition. Fus, Fusarium; Bo, Botrytis; D and E, empty wells; and Fenp, fenpiclonil, as indicated. In FIG. 3, Pep106, peptide 106; Pep107, peptide 107; Pep112, peptide 112; Pep113, peptide 113; Pep114, peptide 114; and Pep115, peptide 115, untreated and 50% EtOH treated were used as negative control conditions, and 100 μM fenpiclonil was used as positive control condition. [Figure 4] Fluorescence quantification of resazurin for Fusarium and Botrytis conidia incubated with 100 μM selected candidate CGI factors. Four replicates of each fungal species were evaluated for each condition. Fus, Fusarium; Bo, Botrytis; D and E, empty wells; and Fenp, fenpiclonil, as indicated. In FIG. 4, Pep106, peptide 106; Pep107, peptide 107; Pep112, peptide 112; Pep113, peptide 113; Pep114, peptide 114; and Pep115, peptide 115, untreated and 50% EtOH treated were used as negative control conditions, and 100 μM fenpiclonil was used as positive control condition. [Diagram 5]1 shows the CGI factor amino acid motif (SEQ ID NO: 1921). The height of the letters in the motif indicates the degree of conservation, with taller letters indicating more conservation. The Y-axis is stack height, which is a representation of the relative entropy of the position, with the height of the letters indicating the estimated probability or degree of conservation, with taller letters being more conserved. For this motif, the predicted probability of a given amino acid occurring at the specific positions listed is as follows: 1st, W: 1.000. 2nd, T: 0.011, E: 0.014, K: 0.025, Q: 0.027, S: 0.040, R: 0.043, G: 0.098, and H: 0.742. 3rd, W: 1.000. 4th, G: 0.047, I: 0.087, V: 0.103, and L: 0.763. 5th, ,A: 0.022, T: 0.040, K: 0.066, E: 0.067, N: 0.071, S: 0.128, R: 0.283, and Q: 0.323. 6th place, I: 0.051, F: 0.171, and L: 0.778. 7th place, E: 0.013, A: 0.015, Y: 0.016, Q: 0.020, M:0.036, F:0.041, S:0.043, G:0.068, D:0.107, R:0.301, and K:0.328. 8th place, N:0. 010, T:0.015, L:0.020, A:0.021, Y:0.025, I:0.025, W:0.031, V:0.039, M:0.04 5, K: 0.089, R: 0.110, and P: 0.556. 9th position, G: 1.000. 10th position, A: 0.034, E: 0.182, and Q: 0.784. 11th position, P: 1.000. 12th position, F: 0.028, L: 0.093, I: 0.182, and M: 0.697. 13th position, Y: 1.000. The upper x-axis indicates the position k of the amino acid in the sequence. The first row of the lower x-axis is the insertion probability, i.e., the probability of observing one or more characters inserted between the character corresponding to position k and the character corresponding to position (k+1). The second row of the lower x-axis is the insertion length, i.e., the expected length of the insertion (if any) following position k. The third row on the bottom x-axis is the occupancy, occ(k), i.e. the probability of observing a character at position k; the probability of observing a gap character or a deletion given the model is [1-occ(k)].This motif is characterized, for example, by having instability only at the last three amino acid residues (positions 11, 12, and / or 13) when the CGI factor polypeptide lacks the Y residue at position 13. [Figure 6A] 4 shows the results of a colorimetric Fusarium viability assay (using resazurin) from three experiments. 2 shows the results of a first experiment in which the natural alpha pheromone from Fusarium spp. (Fusarium ph., WCTWKGQPCW (SEQ ID NO: 2182)), the natural alpha pheromone from Botrytis spp. (Botrytis ph., WCGRPGQPC (SEQ ID NO: 2183)), and the natural alpha pheromone from Saccharomyces cerevisiae (Yeast Ph., WHWLQLKPGQPMY (SEQ ID NO: 2184)), as well as a synthetic peptide (Scr. Yeast 1, WKMGQYHQLPPLW (SEQ ID NO: 2185)), and a modified Saccharomyces cerevisiae alpha pheromone with a C-terminal glycine cap (Yeast Pep-Gly, WHWLQLKPGQPMYG (SEQ ID NO: 2186)) were tested at a concentration of 375 μM. In Figures 6A-6C, the controls used were no treatment, 50% ethanol (negative control), and the fungicide fenpiclonil (positive control). [Figure 6B]2 shows the results of a Fusarium viability colorimetric assay (using resazurin) from three experiments, using the natural alpha pheromone from Fusarium spp. (Fusarium ph., WCTWKGQPCW (SEQ ID NO: 2182)), the natural alpha pheromone from Botrytis spp. (Botrytis ph., WCGRPGQPC (SEQ ID NO: 2183)), and the natural alpha pheromone from Saccharomyces cerevisiae (Yeast Ph., WHWLQLKPGQPMY (SEQ ID NO: 2184)), as well as a synthetic peptide (Scr. Yeast 1, WKMGQYHQLPPLW (SEQ ID NO: 2185)), and a modified Saccharomyces cerevisiae with a C-terminal glycine cap. 6A-6C show the results of a second experiment in which the S. cerevisiae alpha pheromone (Yeast Pep-Gly, WHWLQLKPGQPMYG (SEQ ID NO: 2186)) was tested at a concentration of 375 μM and viability was measured 51 hours after addition of resazurin. In Figures 6A-6C, the controls used were untreated, 50% ethanol (negative control), and the fungicide fenpiclonil (positive control). [Figure 6C]4 shows the results of a colorimetric Fusarium viability assay (using resazurin) from three experiments. The natural alpha pheromone from Fusarium spp. (HH1, WCTWKGQPCW (SEQ ID NO: 2182)), the natural alpha pheromone from Botrytis spp. (HH2, WCGRPGQPC (SEQ ID NO: 2183)), and the natural alpha pheromone from Saccharomyces cerevisiae (HH3, WHWLQLKPGQPMY (SEQ ID NO: 2184)), as well as synthetic peptides (HH31, WKMGQYHQLPPLW (SEQ ID NO: 2185)), a modified Saccharomyces cerevisiae alpha pheromone with a C-terminal glycine cap (HH35, WHWLQLKPGQPMYG (SEQ ID NO: 2186)), a modified Saccharomyces cerevisiae alpha pheromone with an N-terminal glycine cap (HH36, WHWLQLKPGQPMYG (SEQ ID NO: 2187)), and a modified Saccharomyces cerevisiae alpha pheromone with an N-terminal glycine cap (HH37, WHWLQLKPGQPMYG (SEQ ID NO: 2188)). cerevisiae alpha pheromone (HH36, GWHWLQLKPGQPMY (SEQ ID NO: 2187)), a peptide with the sequence of adjacent tandem copies of the Saccharomyces cerevisiae alpha pheromone (HH37, WHWLQLKPGQPMYWHWLQLKPGQPMY (SEQ ID NO: 2188)), and a peptide with adjacent tandem copies of the Saccharomyces cerevisiae alpha pheromone separated by a four glycine linking segment (HH38, WHWLQLKPGQPMYWHWLQLKPGQPMY (SEQ ID NO: 2189)). 6A-6C show the results of a third experiment in which a peptide having the sequence of tandem copies of the S. cerevisiae alpha pheromone (HH38, WHWLQLKPGQPMYGGGGSWHWLQLKPGQPMY (SEQ ID NO: 2189) was tested at concentrations of 175 μM and 375 μM. In FIGS. 6A-6C, the controls used were untreated, 50% ethanol (negative control), and the fungicide fenpiclonil (positive control). [Figure 7]1 shows the results of an experiment to test fungal lesion size on Nicotiana benthamiana leaves following treatment with a Botrytis cinerea conidial suspension followed by 5 mM MES buffer ("MES") or 275 micromolar CGI factor "HH38" (SEQ ID NO: 2189) in 5 mM MES buffer (or nothing added as an "untreated" control). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] Detailed Description Unless otherwise defined, all technical and scientific terms used have the same meaning as commonly understood by those skilled in the art to which this disclosure belongs. Conventional methods, such as those provided in the art and those exemplified in the examples and various general references, are used in the procedures described herein. Unless otherwise specified, the nucleic acid sequences described herein are given in the 5' to 3' direction when read from left to right. The nucleic acid sequences, as specified, may be provided as DNA or RNA, and the disclosure of one necessarily defines the other, as known to those skilled in the art. Furthermore, due to codon degeneracy, different nucleic acid sequences can code for the same polypeptide sequence, and such modified nucleic acid sequences (e.g., for purposes of codon optimization for a given species) are within the scope of this disclosure.

[0011] The term "comprise" is intended to mean "include". Where a term is provided in the singular, the aspects of the invention described by the plural of that term are also intended. As used herein, the term "and / or" should be understood as specifically disclosing each of the multiple specified features or components together with or without the other. Thus, the term "and / or", when used herein in phrases such as "A and / or B", is intended to include "A and B", "A or B", "A" (single), and "B" (single). Similarly, the term "and / or", when used in phrases such as "A, B, and / or C", is intended to include each of the following embodiments: A, B, and C; A, B, or C; A or C; A or B; B or C; A and C; A and B; B and C; A (single); B (single); and C (single).

[0012] The following description sets forth example methods, parameters, etc., however, it should be understood that such description is not intended to limit the scope of the present disclosure, but is instead provided as a description of example embodiments.

[0013] Antifungal or fungicidal peptides Aspects of the present disclosure provide conidial germination inhibitor (CGI) factors, CGI factor precursors, CGI factor fragments, or CGI factor motifs for fungal control, where fungal control includes inhibiting or reducing conidial germination, fungal growth, or fungal reproduction, and fungal control is fungicidal (capable of killing fungi). A "CGI factor fragment" refers to an amino acid sequence that is reduced by one or two amino acids compared to a CGI factor while retaining the function of the CGI factor. A "CGI factor precursor" is a polypeptide that includes at least one copy of a CGI factor (in embodiments, two or more copies of a CGI factor or multiple different CGI factors), and that has been processed to a mature CGI factor, for example, through proteolytic cleavage. CGI factor precursors include precursors that include sequences that are originally encoded in one or more fungal genomes, as well as precursors with synthetic sequences. An "active" CGI factor, CGI factor precursor, or CGI factor fragment refers to a CGI factor, CGI factor precursor, or CGI factor fragment that can inhibit fungal conidial germination activity (conidial germination inhibitory), fungal growth, or fungal reproduction. A "toxic" CGI factor, CGI factor precursor, or CGI factor fragment refers to a CGI factor, CGI factor precursor, or CGI factor fragment that can kill a fungus or reduce the number of viable cells in a population of fungal cells (i.e., fungicidal). A CGI factor, CGI factor precursor, or CGI factor fragment may be active without toxicity, or may be toxic without activity, or may be both active and toxic. Both active and / or toxic CGI factors, CGI factor precursors, or CGI factor fragments are CGI factors, CGI factor precursors, or CGI factor fragments of the present disclosure.

[0014] The CGI element motif comprises the sequence WX1WX2X3X4X5X6GX7PX8Y (SEQ ID NO: 1921), where X1 is selected from the group of T, E, K, Q, S, R, G, and H; X2 is selected from the group of G, I, V, and L; X3 is selected from the group of A, T, K, E, N, S, R, and Q; X4 is selected from the group of I, F, and L; X5 is selected from the group of E, A, Y, Q, M, F, S, G, D, R, and K; X6 is selected from the group of N, T, L, A, Y, I, W, V, M, K, R, and P; X7 is selected from the group of A, E, and Q; and X8 is selected from the group of F, L, I, and M. The CGI factor motifs are SEQ ID NO:1922, SEQ ID NO:1923, SEQ ID NO:1924, SEQ ID NO:1925, SEQ ID NO:1926, SEQ ID NO:1927, SEQ ID NO:1928, SEQ ID NO:1929, SEQ ID NO:1930, SEQ ID NO:1931, SEQ ID NO:1932, SEQ ID NO:1933, SEQ ID NO:1934, SEQ ID NO:1935, SEQ ID NO:1936, SEQ ID NO:1937, SEQ ID NO:1938, SEQ ID NO:1939, SEQ ID NO:1940, SEQ ID NO:1941, SEQ ID NO: 1942, SEQ ID NO:1943, SEQ ID NO:1944, SEQ ID NO:1945, SEQ ID NO:1946, SEQ ID NO:1947, SEQ ID NO:1948, SEQ ID NO:1949, SEQ ID NO:1950, SEQ ID NO:1951, SEQ ID NO:1952, SEQ ID NO:1953, SEQ ID NO:1954, SEQ ID NO:1955, or SEQ ID NO:1956, each of which represents a motif subset of the sequence WX1WX2X3X4X5X6GX7PX8Y (SEQ ID NO:1921).

[0015] In some embodiments, the CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is applied to plants, plant parts, harvested parts of plants, seeds, or planting sites to control any type of fungal plant pathogen. The plants and plant cells are of any species of interest, including dicotyledons and monocotyledons. The plants of interest include row crops, fruit-producing plants and trees, vegetables, trees, and ornamental plants, including ornamental flowers, shrubs, trees, ground covers, and lawns. Examples of commercially important cultivated crops, trees, and plants include alfalfa (Medicago sativa), almonds (Prunus dulcis), apples (Malus x domestica), apricots (Prunus armeniaca, P. brigantine, P. mandshurica, P. mume, P. sibirica), artichokes (Cynara cardunculus var. scolymus), asparagus (Asparagus officinalis), avocados (Persea americana), bananas (Musa spp.), barley (Hordeum vulgare), beans (Phaseolus spp.), blueberries and cranberries (Vaccinium spp.), Brazil nuts (Bertholletia excelsa), cacao (Theobroma cacao), calamansi (Citrus x microcarpa), canola and rapeseed or oilseed rape (Brassica napus), Polish canola (Brassica rapa), and related cruciferous vegetables including broccoli, kale, cabbage, and turnip (Brassica carinata, B. juncea, B. oleracea, B. napus, B. nigra, and B.rapa, and their hybrids), carnation (Dianthus caryophyllus), carrot (Daucus carota sativus), cashew (Anacardium occidentale), cassava (Manihot esculentum), celery (Apium graveolens), cherry (Prunus avium), chestnut (Castanea spp.), chickpea or garbanzo (Cicer arietinum), chicory (Cichorium intybus), chili peppers and hot peppers (Capsicum annuum, C. frutescens, C. chinense, C. pubescens, C. baccatum), chrysanthemum (Chrysanthemum spp.), citron (Citrus medica), coconut (Cocos nucifera), coffee (Coffea arabica, Coffea wild and cultivated coffee spp. including Coffea canephora, and Coffea liberica, cotton (Gossypium hirsutum L.), cowpea (Vigna unguiculata and other Vigna spp.), broad beans (Vicia faba), cucumber (Cucumis sativus), currants and gooseberries (Ribes spp.), dates (Phoenix dactylifera), duckweed (family Lemnoideae), eggplant or aubergine (Solanum melongena), elderberry (Sambucus spp.), eucalyptus (Eucalyptus spp.), flax (Linum usitatissumum L.), geranium (Pelargonium spp.), ginger (Zingiber officinale), ginseng (Panax spp.), grapefruit (Citrus x paradisi), grapes (Vitis spp.), including wine grapes (Vitis vinifera and their hybrids), guava (Psidium guajava), hazelnuts (Corylus avellana, Corylus spp.), hemp and cannabis (Cannabis sativa and Cannabis spp.), hops (Humulus lupulus), horseradish (Armoracia rusticana), iris (Iris spp.), jackfruit (Artocarpus heterophyllus), kiwifruit (Actinidia spp.), kumquats (Citrus japonica), lemons (Citrus limon), lentils (Lens culinaris, lettuce (Lactuca sativa), lime (Citrus spp.), litchi (Litchi chinensis), macadamia (Macadamia spp.), corn (Zea mays L.), mandarin (Citrus reticulata), mango (Mangifera indica), mangosteen (Garcinia mangostana), melon (Cucumis melo), millet (Setaria spp., Echinochloa spp., Eleusine spp., Panicum spp., Pennisetum spp.), oats (Avena sativa), oil palm (Ellis quineensis), okra (Abelmoschus esculentus), olive (Olea europaea), onion (Allium cepa) and other alliums (Allium spp.), orange (Citrus sinensis), papaya (Carica papaya), parsnip (Pastinaca sativa), passion fruit (Passiflora edulis), pecan (Carya illinoinensis), peaches and nectarines (Prunus persica), pears (Pyrus spp.), peas (Pisum sativum), peanuts (Arachis hypogaea), peonies (Paeonia spp.), persimmons (Diospyros kaki), petunias (Petunia spp.), pineapple (Ananas comosus), pistachio (Pistacia vera), plantains (Musa spp.), plums (Prunus domestica), poinsettia (Euphorbia pulcherrima), pomelo (Citrus maxima), poplar (Populus spp.), potato (Solanum tuberosum), pumpkins and squash (Cucurbita pepo, C. maxima, C. moschata), quince (Cydonia oblonga), raspberry (Rubus idaeus, Rubus occidentalis, Rubus spp.), rhubarb (Rheum spp.), rice (Oryza sativa L.), rose (Rosa spp.), rubber (Hevea brasiliensis), rye (Secale cereale), safflower (Carthamus tinctorius L.), satsuma mandarin (Citrus unshiu), sesame seeds (Sesame indium), sorghum (Sorghum bicolor), bitter orange (Citrus x aurantium), soursop (Annona muricata), soybean (Glycine max L.), strawberry (Fragaria spp.), Fragaria x ananassa, sugar beet (Beta vulgaris), sugar cane (Saccharum spp.), sunflower (Helianthus annuus), sweet potato (Ipomoea batatas), tamarind (Tamarindus indica), tangerine (Citrus tangerina), tea (Camellia sinensis), tobacco (Nicotiana tabacum L.), tomatillo (Physalis philadelphica), tomato (Solanum lycopersicum or Lycopersicon esculentum), tulips (Tulipa spp.), walnuts (Juglans spp. L.), watermelon (Citrulus lanatus), wheat (Triticum aestivum, as well as yams (Discorea spp.). Wild relatives of cultivated plants are also of interest.

[0016] Exemplary diseases that may be treated, with the causative pathogens indicated in parentheses, include Alternaria leaf and fruit spot (Alternaria alternata), anthracnose (Colletotrichum acutatum), leaf blight (Seimatosporium lichenicola), leaf rust (Tranzschelia discolor), rot (Cladosporium carpophilum), perforation (Wilsonomyces carpophilus), brown spot (Monilinia laxa, M. fructicola), black sigatoka (Mycosphaerella fisiensis), and sigatoka disease (Mycosphaerella fijiensis), Yellow Sigatoka Disease (Mycosphaerella musicola), Alternaria fruit rot (Alternaria spp.), Anthracnose fruit rot (Colletotrichum gloeosporioides), Botryosphaeria branch blight (Botryosphaeria spp.), Spotted spots and lesions (Mycosphaerella spp.), Septoria spp.), Mummyberry (Monilinia vaccinii-corymbosi), Phoenix brown spot, branch blight and stem canker (Phomopsis vaccinii-corymbosi). vaccinii), powdery mildew (Sphaerotheca spp.), Septoria leaf blight (Septoria spp.), stalk blight (Didymella spp., Phoma spp.), anthracnose (Spaceloma necator, Elsinoe veneta), branch dieback (Botryosphaeria dothidea), Colletotrichum rot (Colletotrichum gloeosporioides), leaf spot and blight (Mycosphaerella spp., Septoria rubi, Sphaerulina rubi), powdery mildew (Sphaerotheca macularis, Microphaera spp., Oidium spp.) spp.), Blackberry Rosette or Double Flower (Cercosporella rubi), Shoot Blight (Didymella applanata), Blackberry Rust (Phragmidium spp.), Anthracnose (Colletotrichum fragariae), Leather Rot (Phytophthora cactorum), Powdery Mildew (Sphaerotheca macularis), Grey Mold on Foliage (Botrytis cinerea), Seedling Root Rot, Basal Stem Rot (Rhizoctonia solani) solani), Cranberry Cottonball (Monilinia oxycocci), Fruit Rot (Physalospora vaccinia, Glomerella cingulata, Coleophoma empetri), Lophodermium Dieback (Lophodermium spp.), Fairy Ring Suppression (Psilocybe spp.), Chlorosis (Alternaria alternata pv citri), Alternaria Leaf and Fruit Spot (Alternaria citri), Anthracnose (Colletotrichum acutatum, C. gloeosporioides), Cercospora Brown Spot (Cercospora spp.), Diplodia Stem Rot (Diplodia natalensis), Yellow Spot (Mycosphaerella citri) citri), Black Spot (Diaporthe citri), Penicillium Decays, Green Mold, Whisker Mold, Blue Mold (Penicillium spp.), Phomopsis Stem Rot (Phomopsis citrii), Post-bloom Fruit Drop (PFD) (Colletotrichum acutatum), Powdery Mildew (Erysiphe spp.), Rot (Elsinoe fawcettii), Sweet orange rot (Elsinoe australis), Black spot (Guignardia citricarpa), Black rot (Guignardia bidwellii), Downy mildew (Plasmopara viticola), Phomopsis cane and leaf spot (Phomopsis viticola), Powdery mildew (Uncinula necator), Botrytis grey mold (Botrytis cinerea), Aspergillus sclerotinia (Aspergillus niger) niger), Pythium blight (Pythium spp.), Stem rot / mildew (Sclerotium rolfsii), Rhizoctonia peg and pod rot (Rhizoctonia solani), Stem rot / mildew (Sclerotium rolfsii), Cylindrocladium black rot (Cylindocladium crotalariae), Pythium black fruit disease (Pythium myriotylum), Alternaria blight (Alternaria alternata), Botryosphaeria tip blight (Botryosphaeria dosidea) dothidea), brown spot (Septoria pistaciarum), rot (Cladosporium carpophilum), Alternaria spot and fruit rot (Alternaria alternata), anthracnose (Colletotrichum prunicola, C. gloeosporioides), brown spot (Septoria pistaciarum), rot (Cladosporium carpophilum), Alternaria spot and fruit rot (Alternaria alternata), anthracnose (Colletotrichum prunicola, C. gloeosporioides), brown spot (Septoria pistaciarum), rot (Cladosporium carpophilum), Alternaria spot and fruit rot (Alternaria alternata), anthracnose (Colletotrichum prunicola, C. gloeosporioides), brown spot (Septoria pistaciarum), rot (Cladosporium carpophilum), brown spot (Septoria pistaciarum), brown spot (Septoria pistaciarum), rot (Cladosporium carpophilum), Alternaria spot and fruit rot (Alternaria alternata), anthracnose (Colletotrichum prunicola, C. gloeosporioides), brown spot (Septoria pistaciarum ...gloeosporioides), leaf rust (Tranzschelia discolor), powdery mildew (Sphaerotheca pannosa), apple powdery mildew (Podosphaera clandestina), perforation (Wilsonomyces carpophilus), Alternaria leaf spot (Alternaria spp.), A. alternata), Ascochyta leaf spot (Ascochyta cynarae), Phyllostica leaf spot (Phyllostica spp.), rust (Uromyces betae), Puccinia helianthii helianthi), White rust (Albugo tragopogonis), Anthracnose (Colletotrichum acutatum), Glomerella cingulata), Eastern filbert wilt (Anisogramma anomale), Late blight (Alternaria alternata), Rot (Cladosporium carpophilum), Brown spot (Septoria pistaciarum), Perforation (Wilsonomyces carpophilus), Blossom rot (Monilinia laxa) laxa), M. fructicola), Powdery Mildew (Erysiphe spp.), Rust (Puccinia spp.), Alternaria black spot (Alternaria brassicae), Blackleg / phoma (Leptosphaeria maculans), Cercospora brown spot (C.brassicicola), foot rot (Rhizoctonia solani), leaf spot and black seed (Alternaria alternata), powdery mildew (Erysiphe polygoni), southern blight (Sclerotium rolfsii), anthracnose leaf blight (Colletotrichum graminicola), gray spot (Cercospora sorghi), northern corn leaf blight (Setosphaeria turcica), northern corn leaf spot (Cochliobolus carbonum), common rust (Puccinia sorghi sorghi), Southern rust (P. polysora), Southern corn leaf blight (Cochliobolus heterostrophus), Eye spot (Aureobasidium zeae), Physoderma brown spot (P. maydis), Yellow leaf blight (Phyllosticta maydis), Ascochyta wilt (A. gossypii), Rust (Puccinia schedonnardi, P. cacabata), Rhizoctonia leaf and stem disease (R. solani), Purple spot (Target spot) (Corynespora cassiicola), southern rot (Sclerotium rolfsii), Rhizoctonia leg rot (R. solani), Cylindrocladium black rot (C. crotalaria)crotalaria), mildew (Sclerotinia minor), early leaf spot (Cercospora arachidicola), late leaf spot (Cercosporidium personatum), web blotch (Phoma arachidicola), rust (Puccinia arachidis), black spot (Leptospherulina crassiasca), southern stem rot (Sclerotium rolfsii) rolfsii), Rhizoctonia leg rot (R. solani), Cylindrocladium black rot (C. crotalaria), White mold (Sclerotinia minor), Anthracnose (Colletotrichum lindemuthianum), Ascochyta rot (A. phaseolorum), Cercospora leaf blight (C. cruenta), Downy mildew (Phytophthora nicotianae), Rust (Uromyces appendiculatas), appendiculatus), anthracnose (late rot) (C. gloeosporoides), mummie berry disease (M. vacciniicorymbosi), rust (Pucciniastrum vaccinii), Septoria brown spot (Septoria albopunctata), downy mildew (Peronospora parasitica), Alternaria leaf rot (A. dauci), Cercospora brown spot (C. carotae),arotae), rhizome rot (Rhizoctonia solani), early blight (Cercospora apii), late blight (Septoria apicola), verticillium brown spot and dry bush, pink rot (Sclerotinia sclerotiorum), Lophodermium leaf / branch blight (L. hypophyllum), upright dieback (Phomopsis vaccinii), anthracnose (Colletotrichum spp.), downy mildew (Pseudoperonospora cubensis). cubensis), purple spot disease (Corynespora cassiico. la), Alternaria leaf blight (A. cucumerina), Alternaria leaf spot (A. alternata), Cercospora brown spot (C. citrullina), Gummy stem blight / vine decline (Didymella bryoniae), Powdery mildew (Sphaerotheca spp. only), Rot (Cladosporium cucumerinum), Anthracnose (Colletotrichum spp.), Botrytis leaf mould (Botrytis cinerea), Cercospora brown spot (Cercospora spp.) spp.), Powdery Mildew (Leveillula taurica), Black Spot (Alternaria porri), Botrytis Crown Rot, Downy Mildew (Peronospora destructor), Early Leaf Spot (Cercospora arachidicola), Late Leaf Spot (Cercosporidium personatum), Black Spot (Leptosphaerulina crassiasca), Black Dot (Colletotrichum coccodes) coccodes), Botrytis vine wilt (B. cinerea), early wilt (Alternaria solani), late wilt (Phytophthora infestans), anthracnose (Colletotrichum truncatum), Cercospora leaf blight (C. kikuchii), soybean black spot (D. phaseolorum), soybean leaf spot (Cercospora sojina), soybean purple spot (C / Kikuchii).kikuchii), Septoria brown spot (S. glycines), Rust (Phakopsora pachyrhizi), Stem canker (Diaporthe phaseolorum), Early blight (Alternaria solani), Gray leaf mold (Fluvia fluva; Cladosporium), Gray spot (Stemphyllium botryosum), Late blight (Phytophthora infestans), Septoria leaf spot (S. lycopersici), Purple spotting (Corynespora cassicola) cassiicola), Alternaria fruit rot (A. alternata), Anthracnose (Colletotrichum spp.), Botrytis grey mold (B. cinerea), Late fruit rot (P. infestans), Rhizoctonia fruit rot (R. solani), Anthracnose (Colletotrichum gloeosporioides), Anthracnose (Colletotrichum acutatum), Blossom / brown rot (Monilinia spp.), Rot (Venturia carpophylla) carpophila), perforation (Wilsonomyces carpophilus), leaf curl (Taphrina deformans), black knot (cherry, plum) (Apiosporina morbosa), cherry leaf spot (Blumeriella jaapii), rot (Cladosporium carpophilum), internal leaf blight (Mycosphaerella spp.and Phaeocryptopus nudus), conifer leaf drop (Phaeocryptopus gaeumannii), internal leaf blight (Mycosphaerella spp. and Phaeocryptopus nudus), Secreloderis branch blight (Gremmeniella abietina), leaf rust (Secreloderis minima), powdery mildew (Erysiphe necator), Alternaria rot (A. alternata), angular spot (Mycosphearella angulata), angulata), anthracnose (Elsinoe ampelina), black rot (Guignardia bidwellii), leaf blight (Pseudocercospora vitis), homopsis cane leaf spot (P. viticola), Rotbrenner (Pseudopezicula tracheiphila), Septoria leaf spot (S. ampelina), apple rot (Venturia inaequalis), pear rot (V. piris), Alternaria spotted leaf spot, Alternaria black rot (Alternaria spp. spp.), apple and pear rust (Gymnosporangium juniper-virginianae), powdery mildew (Podosphaera leucotricha), quince rust (Gymnosporangium spp.)) Apple sooty spot, bitter rot (Glomerella cingulata), black rot (Botryosphaeria obtusa), black spot (Mycosphaerella pomi), white rot (Botryosphaeria dothidea), Alternaria rot and surface mold diseases, bitter rot, blue mold, bull's eye rot, gray mold, Phacidiopycnis rot, Rhizopus rot, spot rot, Sphaeropsis rot, white rot, damping off (Pythium spp.), root rot (Phytophthora spp.) spp.), Leather rot (P. cactorum), Root rot (P. fragariae), Vascular collapse (P. cactorum), Stem base rot (Phytophthora spp.), Sclerotinia rot (Phytophthora capsici), Downy mildew (Peronospora effusa; P. farinosa), White rust (Albugo occidentalis), Pink rot (Phytophthora erythroseptica), erythroseptica), Pythium wilt, Pythium seedling disease (Pythium spp.), Soybean stem rot (Phytophthora megasperma), Pythium wilt (Pythium spp.), Collar rot, Sclerotinia rot, Root rot (Phytophthora spp.), Sclerotinia rot, Root rot (Phytophthora spp.), root rot (Phytophthora cinnamomi), downy mildew (Peronospora parasitica), brown rot, citrus stem rot, gum disease, root rot, stem canker (Phytophthora spp., or downy mildew (Bremia lactucae). From an agricultural or horticultural point of view, and for the purposes of this application, some of the pathogens and diseases listed above are considered "fungal", although the causative pathogens are technically classified as Pythion spp., Phytophthora spp., Peronospora spp., Plasmopara spp., spp.), Albugo spp., and Bremia spp. are oomycetes (phylum Oomycota), including, but not limited to:

[0017] When applied to harvested plant parts (also referred to herein as post-harvest), application may be by various treatment methods, such as dipping, dripping, drench, spraying, or fog. In alternative embodiments, harvested plant parts have a composition containing CGI factors, CGI factor precursors, or CGI factor fragments applied to them in a film or membrane, or are packaged in a container containing CGI factors, CGI factor precursors, or CGI factor fragments. Such treatments, compositions, and containers are further useful for protecting food (e.g., processed foods such as bakery products or processed fruits or vegetables) from fungal growth and spoilage. Any of the above-mentioned plants or plant parts may be treated post-harvest.In some embodiments, the plants that are post-harvest treated are alfalfa, almonds, apples, apricots, artichokes, asparagus, avocados, bananas, barley, legumes, blueberries and cranberries, Brazil nuts, cacao, calamansi, canola and rapeseed or oilseed rape, Polish canola, and related cruciferous vegetables including broccoli, kale, cabbage, and turnips, carnations, carrots, cashews, cassava, celery, cherries, chestnuts, chickpeas or garbanzo beans, chicory, chili peppers and hot peppers, chrysanthemums, citrons, coconuts, coffee, cotton, cowpeas, broad beans (Vicia faba), cucumbers (Cucumis sativus), currants and gooseberries, dates, duckweed, eggplant or aubergine, elderberry, eucalyptus, flax, geranium, ginger, ginseng, grapefruit, grapes including wine grapes, guava, hazelnuts, hemp and cannabis, hops, horseradish, iris, jackfruit, kiwi fruit, kumquat, lemon, lentil, lettuce, lime, lychee, macadamia, corn or maize, mandarin, mango, mangosteen, melon, millet, oats, oil palm, okra, olives, onions and other alliums, orange, papaya, parsnips fruit, passion fruit, pecans, peaches and nectarines, pears, peas, peanuts, peonies, persimmons, petunias, pineapples, pistachios, plantains, plums, poinsettias, pomelos, poplars, potatoes, pumpkins and squash, quince, raspberries, rhubarb, rice, roses, rubber, rye, safflower, satsuma mandarins, sesame seeds, sorghum, bitter orange, soursop, soybeans, strawberries, sugar beets, sugar cane, sunflowers, sweet potatoes, tamarind, tangerines, tea, tobacco, tomatillo, tomatoes, tulips, walnuts, watermelon, wheat, and yams.

[0018] In some embodiments, the CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is active and / or toxic to structural element fungal pathogens (e.g., fungal pathogens that infect or damage human constructed structures such as buildings or other human created man-made objects, or components thereof). In some embodiments, it inhibits the growth or reproduction of, or is toxic to, fungi that collectively provide wood or other materials useful in human constructed structures or man-made objects (examples include wood-rotting fungi that cause brown rot, white rot, or soft rot, or fungi that cause dry rot in human constructed structures or buildings).In some embodiments, the structural element fungal pathogen is a dry rot fungus (Serpula lacrymans), a cellulolytic rot fungus (Coniphora puteana), a wet rot fungus (Antrodia vaillantii, A. xantha, Asterostroma spp., Donkioporia expansa, Paxillus panuoides, Phellinus contignuus, Tyromyces placentus, or a fungus that colonizes water-invaded structural materials, such as Penicillium chrysogenum. chrysogenum, Aspergillus versicolor, Chaetomium spp., Acremonium spp., Ulocladium spp., Stachybotrys spp., Arthrinium phaeospermum, Aureobasidium pullulans, Cladosporium herbarum, Trichoderma spp., Aspergillus fumigatus, Aspergillus melleus melleus, Aspergillus niger, Aspergillus ochraceus, Mucor racemosus, or Mucor spinosus.

[0019] Recombinant DNA constructs and vectors Aspects of the disclosure include recombinant DNA constructs comprising a heterologous promoter operably linked to a nucleic acid molecule comprising a nucleotide sequence encoding a conidial germination inhibition (CGI) factor, a CGI factor precursor, or a CGI factor fragment, the nucleotide sequence being selected from the group consisting of: (a) SEQ ID NO:961, SEQ ID NO:962, SEQ ID NO:963, SEQ ID NO:964, SEQ ID NO:965, SEQ ID NO:966, SEQ ID NO:967, SEQ ID NO:968, SEQ ID NO:969, SEQ ID NO:970, SEQ ID NO:971, SEQ ID NO:972, SEQ ID NO:973, SEQ ID NO:974, SEQ ID NO:975, SEQ ID NO:976, SEQ ID NO:977, SEQ ID NO: No. 978, SEQ ID NO: 979, SEQ ID NO: 980, SEQ ID NO: 981, SEQ ID NO: 982, SEQ ID NO: 983, SEQ ID NO: 984, SEQ ID NO: 985, SEQ ID NO: 986, SEQ ID NO: 987, SEQ ID NO: 988, SEQ ID NO: 989, SEQ ID NO: 990, SEQ ID NO: 991, SEQ ID NO: 992, SEQ ID NO: 993, SEQ ID NO: 994, SEQ ID NO: 995, SEQ ID NO: 996, SEQ ID NO: 997, SEQ ID NO: 998, SEQ ID NO: 999, SEQ ID NO: 1000, SEQ ID NO: 1001, SEQ ID NO: 1002, SEQ ID NO: 1003, SEQ ID NO: 1004, SEQ ID NO: 1005, SEQ ID NO: 1006, SEQ ID NO: 1007, SEQ ID NO: 008, SEQ ID NO:1009, SEQ ID NO:1010, SEQ ID NO:1011, SEQ ID NO:1012, SEQ ID NO:1013, SEQ ID NO:1014, SEQ ID NO:1015, SEQ ID NO:1016, SEQ ID NO:1017, SEQ ID NO:1018, SEQ ID NO:1019, SEQ ID NO:1020, SEQ ID NO:1021, SEQ ID NO:1022, SEQ ID NO:1023, SEQ ID NO:1024, SEQ ID NO:1025, SEQ ID NO:1026, SEQ ID NO:1027, SEQ ID NO:1028, SEQ ID NO:1029, SEQ ID NO:1030, SEQ ID NO:1031, SEQ ID NO:1032, SEQ ID NO:1033, SEQ ID NO:1034, SEQ ID NO:1035, SEQ ID NO: No. 1036, SEQ ID NO. 1037, SEQ ID NO. 1038, SEQ ID NO. 1039, SEQ ID NO. 1040, SEQ ID NO. 1041, SEQ ID NO. 1042, SEQ ID NO. 1043, SEQ ID NO. 1044, SEQ ID NO. 1045, SEQ ID NO. 1046, SEQ ID NO. 1047, SEQ ID NO. 1048, SEQ ID NO. 1049, SEQ ID NO. 1050, SEQ ID NO. 1051, SEQ ID NO. 1052, SEQ ID NO. 1053, SEQ ID NO. 1054, SEQ ID NO. 1055, SEQ ID NO. 1056, SEQ ID NO. 1057, SEQ ID NO. 1058, SEQ ID NO. 1059, SEQ ID NO. 1060, SEQ ID NO. 1061, SEQ ID NO. 1062, SEQ ID NO. 1063,SEQ ID NO:1064, SEQ ID NO:1065, SEQ ID NO:1066, SEQ ID NO:1067, SEQ ID NO:1068, SEQ ID NO:1069, SEQ ID NO:1070, SEQ ID NO:1071, SEQ ID NO:1072, SEQ ID NO:1073, SEQ ID NO:1074, SEQ ID NO:1075, SEQ ID NO:1076, SEQ ID NO:1077, SEQ ID NO:1078, SEQ ID NO:1079, SEQ ID NO:1080, SEQ ID NO:1081, SEQ ID NO:1082, SEQ ID NO:1083, SEQ ID NO:1084, SEQ ID NO:1085, SEQ ID NO:1086, SEQ ID NO:1087, SEQ ID NO:1088, SEQ ID NO:1089, SEQ ID NO:1090, SEQ ID NO:10 91, SEQ ID NO:1092, SEQ ID NO:1093, SEQ ID NO:1094, SEQ ID NO:1095, SEQ ID NO:1096, SEQ ID NO:1097, SEQ ID NO:1098, SEQ ID NO:1099, SEQ ID NO:1100, SEQ ID NO:1101, SEQ ID NO:1102, SEQ ID NO:1103, SEQ ID NO:1104, SEQ ID NO:1105, SEQ ID NO:1106, SEQ ID NO:1107, SEQ ID NO:1108, SEQ ID NO:1109, SEQ ID NO:1110, SEQ ID NO:1111, SEQ ID NO:1112, SEQ ID NO:1113, SEQ ID NO:1114, SEQ ID NO:1115, SEQ ID NO:1116, SEQ ID NO:1117, SEQ ID NO:1118, 1119, SEQ ID NO:1120, SEQ ID NO:1121, SEQ ID NO:1122, SEQ ID NO:1123, SEQ ID NO:1124, SEQ ID NO:1125, SEQ ID NO:1126, SEQ ID NO:1127, SEQ ID NO:1128, SEQ ID NO:1129, SEQ ID NO:1130, SEQ ID NO:1131, SEQ ID NO:1132, SEQ ID NO:1133, SEQ ID NO:1134, SEQ ID NO:1135, SEQ ID NO:1136, SEQ ID NO:1137, SEQ ID NO:1138, SEQ ID NO:1139, SEQ ID NO:1140, SEQ ID NO:1141, SEQ ID NO:1142, SEQ ID NO:1143, SEQ ID NO:1144, SEQ ID NO:1145, SEQ ID NO:1146, SEQ ID NO: No. 1147, SEQ ID NO. 1148, SEQ ID NO. 1149, SEQ ID NO. 1150, SEQ ID NO. 1151, SEQ ID NO. 1152, SEQ ID NO. 1153, SEQ ID NO. 1154, SEQ ID NO. 1155, SEQ ID NO. 1156, SEQ ID NO. 1157, SEQ ID NO. 1158, SEQ ID NO. 1159, SEQ ID NO. 1160, SEQ ID NO. 1161, SEQ ID NO. 1162, SEQ ID NO. 1163, SEQ ID NO. 1164, SEQ ID NO. 1165, SEQ ID NO. 1166, SEQ ID NO. 1167, SEQ ID NO. 1168, SEQ ID NO. 1169, SEQ ID NO. 1170, SEQ ID NO. 1171, SEQ ID NO. 1172, SEQ ID NO. 1173, SEQ ID NO. 1174,SEQ ID NO:1175, SEQ ID NO:1176, SEQ ID NO:1177, SEQ ID NO:1178, SEQ ID NO:1179, SEQ ID NO:1180, SEQ ID NO:1181, SEQ ID NO:1182, SEQ ID NO:1183, SEQ ID NO:1184, SEQ ID NO:1185, SEQ ID NO:1186, SEQ ID NO:1187, SEQ ID NO:1188, SEQ ID NO:1189, SEQ ID NO:1190, SEQ ID NO:1191, SEQ ID NO:1192, SEQ ID NO:1193, SEQ ID NO:1194, SEQ ID NO:1195, SEQ ID NO:1196, SEQ ID NO:1197, SEQ ID NO:1198, SEQ ID NO:1199, SEQ ID NO:1200, SEQ ID NO:1201, SEQ ID NO:12 02, SEQ ID NO:1203, SEQ ID NO:1204, SEQ ID NO:1205, SEQ ID NO:1206, SEQ ID NO:1207, SEQ ID NO:1208, SEQ ID NO:1209, SEQ ID NO:1210, SEQ ID NO:1211, SEQ ID NO:1212, SEQ ID NO:1213, SEQ ID NO:1214, SEQ ID NO:1215, SEQ ID NO:1216, SEQ ID NO:1217, SEQ ID NO:1218, SEQ ID NO:1219, SEQ ID NO:1220, SEQ ID NO:1221, SEQ ID NO:1222, SEQ ID NO:1223, SEQ ID NO:1224, SEQ ID NO:1225, SEQ ID NO:1226, SEQ ID NO:1227, SEQ ID NO:1228, SEQ ID NO:1229, 1230, SEQ ID NO:1231, SEQ ID NO:1232, SEQ ID NO:1233, SEQ ID NO:1234, SEQ ID NO:1235, SEQ ID NO:1236, SEQ ID NO:1237, SEQ ID NO:1238, SEQ ID NO:1239, SEQ ID NO:1240, SEQ ID NO:1241, SEQ ID NO:1242, SEQ ID NO:1243, SEQ ID NO:1244, SEQ ID NO:1245, SEQ ID NO:1246, SEQ ID NO:1247, SEQ ID NO:1248, SEQ ID NO:1249, SEQ ID NO:1250, SEQ ID NO:1251, SEQ ID NO:1252, SEQ ID NO:1253, SEQ ID NO:1254, SEQ ID NO:1255, SEQ ID NO:1256, SEQ ID NO:1257, SEQ ID NO: No. 1258, SEQ ID NO. 1259, SEQ ID NO. 1260, SEQ ID NO. 1261, SEQ ID NO. 1262, SEQ ID NO. 1263, SEQ ID NO. 1264, SEQ ID NO. 1265, SEQ ID NO. 1266, SEQ ID NO. 1267, SEQ ID NO. 1268, SEQ ID NO. 1269, SEQ ID NO. 1270, SEQ ID NO. 1271, SEQ ID NO. 1272, SEQ ID NO. 1273, SEQ ID NO. 1274, SEQ ID NO. 1275, SEQ ID NO. 1276, SEQ ID NO. 1277, SEQ ID NO. 1278, SEQ ID NO. 1279, SEQ ID NO. 1280, SEQ ID NO. 1281, SEQ ID NO. 1282, SEQ ID NO. 1283, SEQ ID NO. 1284, SEQ ID NO. 1285,SEQ ID NO:1286, SEQ ID NO:1287, SEQ ID NO:1288, SEQ ID NO:1289, SEQ ID NO:1290, SEQ ID NO:1291, SEQ ID NO:1292, SEQ ID NO:1293, SEQ ID NO:1294, SEQ ID NO:1295, SEQ ID NO:1296, SEQ ID NO:1297, SEQ ID NO:1298, SEQ ID NO:1299, SEQ ID NO:1300, SEQ ID NO:1301, SEQ ID NO:1302, SEQ ID NO:1303, SEQ ID NO:1304, SEQ ID NO:1305, SEQ ID NO:1306, SEQ ID NO:1307, SEQ ID NO:1308, SEQ ID NO:1309, SEQ ID NO:1310, SEQ ID NO:1311, SEQ ID NO:1312, SEQ ID NO:13 13, SEQ ID NO:1314, SEQ ID NO:1315, SEQ ID NO:1316, SEQ ID NO:1317, SEQ ID NO:1318, SEQ ID NO:1319, SEQ ID NO:1320, SEQ ID NO:1321, SEQ ID NO:1322, SEQ ID NO:1323, SEQ ID NO:1324, SEQ ID NO:1325, SEQ ID NO:1326, SEQ ID NO:1327, SEQ ID NO:1328, SEQ ID NO:1329, SEQ ID NO:1330, SEQ ID NO:1331, SEQ ID NO:1332, SEQ ID NO:1333, SEQ ID NO:1334, SEQ ID NO:1335, SEQ ID NO:1336, SEQ ID NO:1337, SEQ ID NO:1338, SEQ ID NO:1339, SEQ ID NO:1340, 1341, SEQ ID NO:1342, SEQ ID NO:1343, SEQ ID NO:1344, SEQ ID NO:1345, SEQ ID NO:1346, SEQ ID NO:1347, SEQ ID NO:1348, SEQ ID NO:1349, SEQ ID NO:1350, SEQ ID NO:1351, SEQ ID NO:1352, SEQ ID NO:1353, SEQ ID NO:1354, SEQ ID NO:1355, SEQ ID NO:1356, SEQ ID NO:1357, SEQ ID NO:1358, SEQ ID NO:1359, SEQ ID NO:1360, SEQ ID NO:1361, SEQ ID NO:1362, SEQ ID NO:1363, SEQ ID NO:1364, SEQ ID NO:1365, SEQ ID NO:1366, SEQ ID NO:1367, SEQ ID NO:1368, No. 1369, SEQ ID NO: 1370, SEQ ID NO: 1371, SEQ ID NO: 1372, SEQ ID NO: 1373, SEQ ID NO: 1374, SEQ ID NO: 1375, SEQ ID NO: 1376, SEQ ID NO: 1377, SEQ ID NO: 1378, SEQ ID NO: 1379, SEQ ID NO: 1380, SEQ ID NO: 1381, SEQ ID NO: 1382, SEQ ID NO: 1383, SEQ ID NO: 1384, SEQ ID NO: 1385, SEQ ID NO: 1386, SEQ ID NO: 1387, SEQ ID NO: 1388, SEQ ID NO: 1389, SEQ ID NO: 1390, SEQ ID NO: 1391, SEQ ID NO: 1392, SEQ ID NO: 1393, SEQ ID NO: 1394, SEQ ID NO: 1395, SEQ ID NO: 1396,SEQ ID NO:1397, SEQ ID NO:1398, SEQ ID NO:1399, SEQ ID NO:1400, SEQ ID NO:1401, SEQ ID NO:1402, SEQ ID NO:1403, SEQ ID NO:1404, SEQ ID NO:1405, SEQ ID NO:1406, SEQ ID NO:1407, SEQ ID NO:1408, SEQ ID NO:1409, SEQ ID NO:1410, SEQ ID NO:1411, SEQ ID NO:1412, SEQ ID NO:1413, SEQ ID NO:1414, SEQ ID NO:1415, SEQ ID NO:1416, SEQ ID NO:1417, SEQ ID NO:1418, SEQ ID NO:1419, SEQ ID NO:1420, SEQ ID NO:1421, SEQ ID NO:1422, SEQ ID NO:1423, 24, SEQ ID NO:1425, SEQ ID NO:1426, SEQ ID NO:1427, SEQ ID NO:1428, SEQ ID NO:1429, SEQ ID NO:1430, SEQ ID NO:1431, SEQ ID NO:1432, SEQ ID NO:1433, SEQ ID NO:1434, SEQ ID NO:1435, SEQ ID NO:1436, SEQ ID NO:1437, SEQ ID NO:1438, SEQ ID NO:1439, SEQ ID NO:1440, SEQ ID NO:1441, SEQ ID NO:1442, SEQ ID NO:1443, SEQ ID NO:1444, SEQ ID NO:1445, SEQ ID NO:1446, SEQ ID NO:1447, SEQ ID NO:1448, SEQ ID NO:1449, SEQ ID NO:1450, SEQ ID NO:1451, 1452, SEQ ID NO:1453, SEQ ID NO:1454, SEQ ID NO:1455, SEQ ID NO:1456, SEQ ID NO:1457, SEQ ID NO:1458, SEQ ID NO:1459, SEQ ID NO:1460, SEQ ID NO:1461, SEQ ID NO:1462, SEQ ID NO:1463, SEQ ID NO:1464, SEQ ID NO:1465, SEQ ID NO:1466, SEQ ID NO:1467, SEQ ID NO:1468, SEQ ID NO:1469, SEQ ID NO:1470, SEQ ID NO:1471, SEQ ID NO:1472, SEQ ID NO:1473, SEQ ID NO:1474, SEQ ID NO:1475, SEQ ID NO:1476, SEQ ID NO:1477, SEQ ID NO:1478, SEQ ID NO:1479, SEQ ID NO: No. 1480, SEQ ID NO. 1481, SEQ ID NO. 1482, SEQ ID NO. 1483, SEQ ID NO. 1484, SEQ ID NO. 1485, SEQ ID NO. 1486, SEQ ID NO. 1487, SEQ ID NO. 1488, SEQ ID NO. 1489, SEQ ID NO. 1490, SEQ ID NO. 1491, SEQ ID NO. 1492, SEQ ID NO. 1493, SEQ ID NO. 1494, SEQ ID NO. 1495, SEQ ID NO. 1496, SEQ ID NO. 1497, SEQ ID NO. 1498, SEQ ID NO. 1499, SEQ ID NO. 1500, SEQ ID NO. 1501, SEQ ID NO. 1502, SEQ ID NO. 1503, SEQ ID NO. 1504, SEQ ID NO. 1505, SEQ ID NO. 1506, SEQ ID NO. 1507,SEQ ID NO:1508, SEQ ID NO:1509, SEQ ID NO:1510, SEQ ID NO:1511, SEQ ID NO:1512, SEQ ID NO:1513, SEQ ID NO:1514, SEQ ID NO:1515, SEQ ID NO:1516, SEQ ID NO:1517, SEQ ID NO:1518, SEQ ID NO:1519, SEQ ID NO:1520, SEQ ID NO:1521, SEQ ID NO:1522, SEQ ID NO:1523, SEQ ID NO:1524, SEQ ID NO:1525, SEQ ID NO:1526, SEQ ID NO:1527, SEQ ID NO:1528, SEQ ID NO:1529, SEQ ID NO:1530, SEQ ID NO:1531, SEQ ID NO:1532, SEQ ID NO:1533, SEQ ID NO:1534, SEQ ID NO:1535, SEQ ID NO:1536, SEQ ID NO:1537, SEQ ID NO:1538, SEQ ID NO:1539, SEQ ID NO:1540, SEQ ID NO:1541, SEQ ID NO:1542, SEQ ID NO:1543, SEQ ID NO:1544, SEQ ID NO:1545, SEQ ID NO:1546, SEQ ID NO:1547, SEQ ID NO:1548, 49, SEQ ID NO:1550, SEQ ID NO:1551, SEQ ID NO:1552, SEQ ID NO:1553, SEQ ID NO:1554, SEQ ID NO:1555, SEQ ID NO:1556, SEQ ID NO:1557, SEQ ID NO:1558, SEQ ID NO:1559, SEQ ID NO:1560, SEQ ID NO:1561, SEQ ID NO:1562, SEQ ID NO:1563, SEQ ID NO:1564, SEQ ID NO:1565, SEQ ID NO:1566, SEQ ID NO:1567, SEQ ID NO:1568, SEQ ID NO:1569, SEQ ID NO:1570, SEQ ID NO:1571, SEQ ID NO:1572, SEQ ID NO:1573, SEQ ID NO:1574, SEQ ID NO:1575, SEQ ID NO:1576, 1577, SEQ ID NO:1578, SEQ ID NO:1579, SEQ ID NO:1580, SEQ ID NO:1581, SEQ ID NO:1582, SEQ ID NO:1583, SEQ ID NO:1584, SEQ ID NO:1585, SEQ ID NO:1586, SEQ ID NO:1587, SEQ ID NO:1588, SEQ ID NO:1589, SEQ ID NO:1590, SEQ ID NO:1591, SEQ ID NO:1592, SEQ ID NO:1593, SEQ ID NO:1594, SEQ ID NO:1595, SEQ ID NO:1596, SEQ ID NO:1597, SEQ ID NO:1598, SEQ ID NO:1599, SEQ ID NO:1600, SEQ ID NO:1601, SEQ ID NO:1602, SEQ ID NO:1603, SEQ ID NO:1604, SEQ ID NO: No. 1605, SEQ ID NO. 1606, SEQ ID NO. 1607, SEQ ID NO. 1608, SEQ ID NO. 1609, SEQ ID NO. 1610, SEQ ID NO. 1611, SEQ ID NO. 1612, SEQ ID NO. 1613, SEQ ID NO. 1614, SEQ ID NO. 1615, SEQ ID NO. 1616, SEQ ID NO. 1617, SEQ ID NO. 1618, SEQ ID NO. 1619, SEQ ID NO. 1620, SEQ ID NO. 1621, SEQ ID NO. 1622, SEQ ID NO. 1623, SEQ ID NO. 1624, SEQ ID NO. 1625, SEQ ID NO. 1626, SEQ ID NO. 1627, SEQ ID NO. 1628, SEQ ID NO. 1629, SEQ ID NO. 1630, SEQ ID NO. 1631, SEQ ID NO. 1632,SEQ ID NO:1633, SEQ ID NO:1634, SEQ ID NO:1635, SEQ ID NO:1636, SEQ ID NO:1637, SEQ ID NO:1638, SEQ ID NO:1639, SEQ ID NO:1640, SEQ ID NO:1641, SEQ ID NO:1642, SEQ ID NO:1643, SEQ ID NO:1644, SEQ ID NO:1645, SEQ ID NO:1646, SEQ ID NO:1647, SEQ ID NO:1648, SEQ ID NO:1649, SEQ ID NO:1650, SEQ ID NO:1651, SEQ ID NO:1652, SEQ ID NO:1653, SEQ ID NO:1654, SEQ ID NO:1655, SEQ ID NO:1656, SEQ ID NO:1657, SEQ ID NO:1658, SEQ ID NO:1659, 60, SEQ ID NO:1661, SEQ ID NO:1662, SEQ ID NO:1663, SEQ ID NO:1664, SEQ ID NO:1665, SEQ ID NO:1666, SEQ ID NO:1667, SEQ ID NO:1668, SEQ ID NO:1669, SEQ ID NO:1670, SEQ ID NO:1671, SEQ ID NO:1672, SEQ ID NO:1673, SEQ ID NO:1674, SEQ ID NO:1675, SEQ ID NO:1676, SEQ ID NO:1677, SEQ ID NO:1678, SEQ ID NO:1679, SEQ ID NO:1680, SEQ ID NO:1681, SEQ ID NO:1682, SEQ ID NO:1683, SEQ ID NO:1684, SEQ ID NO:1685, SEQ ID NO:1686, SEQ ID NO:1687, 1688, SEQ ID NO:1689, SEQ ID NO:1690, SEQ ID NO:1691, SEQ ID NO:1692, SEQ ID NO:1693, SEQ ID NO:1694, SEQ ID NO:1695, SEQ ID NO:1696, SEQ ID NO:1697, SEQ ID NO:1698, SEQ ID NO:1699, SEQ ID NO:1700, SEQ ID NO:1701, SEQ ID NO:1702, SEQ ID NO:1703, SEQ ID NO:1704, SEQ ID NO:1705, SEQ ID NO:1706, SEQ ID NO:1707, SEQ ID NO:1708, SEQ ID NO:1709, SEQ ID NO:1710, SEQ ID NO:1711, SEQ ID NO:1712, SEQ ID NO:1713, SEQ ID NO:1714, SEQ ID NO:1715, SEQ ID NO: No. 1716, SEQ ID NO: 1717, SEQ ID NO: 1718, SEQ ID NO: 1719, SEQ ID NO: 1720, SEQ ID NO: 1721, SEQ ID NO: 1722, SEQ ID NO: 1723, SEQ ID NO: 1724, SEQ ID NO: 1725, SEQ ID NO: 1726, SEQ ID NO: 1727, SEQ ID NO: 1728, SEQ ID NO: 1729, SEQ ID NO: 1730, SEQ ID NO: 1731, SEQ ID NO: 1732, SEQ ID NO: 1733, SEQ ID NO: 1734, SEQ ID NO: 1735, SEQ ID NO: 1736, SEQ ID NO: 1737, SEQ ID NO: 1738, SEQ ID NO: 1739, SEQ ID NO: 1740, SEQ ID NO: 1741, SEQ ID NO: 1742, SEQ ID NO: 1743,SEQ ID NO:1744, SEQ ID NO:1745, SEQ ID NO:1746, SEQ ID NO:1747, SEQ ID NO:1748, SEQ ID NO:1749, SEQ ID NO:1750, SEQ ID NO:1751, SEQ ID NO:1752, SEQ ID NO:1753, SEQ ID NO:1754, SEQ ID NO:1755, SEQ ID NO:1756, SEQ ID NO:1757, SEQ ID NO:1758, SEQ ID NO:1759, SEQ ID NO:1760, SEQ ID NO:1761, SEQ ID NO:1762, SEQ ID NO:1763, SEQ ID NO:1764, SEQ ID NO:1765, SEQ ID NO:1766, SEQ ID NO:1767, SEQ ID NO:1768, SEQ ID NO:1769, SEQ ID NO:1770, 71, SEQ ID NO:1772, SEQ ID NO:1773, SEQ ID NO:1774, SEQ ID NO:1775, SEQ ID NO:1776, SEQ ID NO:1777, SEQ ID NO:1778, SEQ ID NO:1779, SEQ ID NO:1780, SEQ ID NO:1781, SEQ ID NO:1782, SEQ ID NO:1783, SEQ ID NO:1784, SEQ ID NO:1785, SEQ ID NO:1786, SEQ ID NO:1787, SEQ ID NO:1788, SEQ ID NO:1789, SEQ ID NO:1790, SEQ ID NO:1791, SEQ ID NO:1792, SEQ ID NO:1793, SEQ ID NO:1794, SEQ ID NO:1795, SEQ ID NO:1796, SEQ ID NO:1797, SEQ ID NO:1798, 1799, SEQ ID NO:1800, SEQ ID NO:1801, SEQ ID NO:1802, SEQ ID NO:1803, SEQ ID NO:1804, SEQ ID NO:1805, SEQ ID NO:1806, SEQ ID NO:1807, SEQ ID NO:1808, SEQ ID NO:1809, SEQ ID NO:1810, SEQ ID NO:1811, SEQ ID NO:1812, SEQ ID NO:1813, SEQ ID NO:1814, SEQ ID NO:1815, SEQ ID NO:1816, SEQ ID NO:1817, SEQ ID NO:1818, SEQ ID NO:1819, SEQ ID NO:1820, SEQ ID NO:1821, SEQ ID NO:1822, SEQ ID NO:1823, SEQ ID NO:1824, SEQ ID NO:1825, SEQ ID NO:1826, SEQ ID NO:1827, SEQ ID NO:1829, SEQ ID NO:1830, SEQ ID NO:1831, SEQ ID NO:1832, SEQ ID NO:1833, SEQ ID NO:1834, SEQ ID NO:1835, SEQ ID NO:1836, SEQ ID NO:1837, SEQ ID NO:1838, SEQ ID NO:1839, SEQ ID NO:1840, SEQ ID NO:1841, SEQ ID NO:1842, SEQ ID NO:1843, SEQ ID NO:1844, SEQ ID NO:1845, SEQ ID NO:1846, SEQ ID NO:1847, SEQ ID NO:1848, SEQ ID NO:1849, SEQ ID NO:1850, SEQ ID NO: No. 1827, SEQ ID NO. 1828, SEQ ID NO. 1829, SEQ ID NO. 1830, SEQ ID NO. 1831, SEQ ID NO. 1832, SEQ ID NO. 1833, SEQ ID NO. 1834, SEQ ID NO. 1835, SEQ ID NO. 1836, SEQ ID NO. 1837, SEQ ID NO. 1838, SEQ ID NO. 1839, SEQ ID NO. 1840, SEQ ID NO. 1841, SEQ ID NO. 1842, SEQ ID NO. 1843, SEQ ID NO. 1844, SEQ ID NO. 1845, SEQ ID NO. 1846, SEQ ID NO. 1847, SEQ ID NO. 1848, SEQ ID NO. 1849, SEQ ID NO. 1850, SEQ ID NO. 1851, SEQ ID NO. 1852, SEQ ID NO. 1853, SEQ ID NO. 1854,SEQ ID NO:1855, SEQ ID NO:1856, SEQ ID NO:1857, SEQ ID NO:1858, SEQ ID NO:1859, SEQ ID NO:1860, SEQ ID NO:1861, SEQ ID NO:1862, SEQ ID NO:1863, SEQ ID NO:1864, SEQ ID NO:1865, SEQ ID NO:1866, SEQ ID NO:1867, SEQ ID NO:1868, SEQ ID NO:1869, SEQ ID NO:1870, SEQ ID NO:1871, SEQ ID NO:1872, SEQ ID NO:1873, SEQ ID NO:1874, SEQ ID NO:1875, SEQ ID NO:1876, SEQ ID NO:1877, SEQ ID NO:1878, SEQ ID NO:1879, SEQ ID NO:1880, SEQ ID NO:1881, SEQ ID NO:18 82, SEQ ID NO:1883, SEQ ID NO:1884, SEQ ID NO:1885, SEQ ID NO:1886, SEQ ID NO:1887, SEQ ID NO:1888, SEQ ID NO:1889, SEQ ID NO:1890, SEQ ID NO:1891, SEQ ID NO:1892, SEQ ID NO:1893, SEQ ID NO:1894, SEQ ID NO:1895, SEQ ID NO:1896, SEQ ID NO:1897, SEQ ID NO:1898, SEQ ID NO:1899, SEQ ID NO:1900, SEQ ID NO:1901, SEQ ID NO:1902, SEQ ID NO:1903, SEQ ID NO:1904, SEQ ID NO:1905, SEQ ID NO:1906, SEQ ID NO:1907, SEQ ID NO:1908, SEQ ID NO:1909, 1910, SEQ ID NO:1911, SEQ ID NO:1912, SEQ ID NO:1913, SEQ ID NO:1914, SEQ ID NO:1915, SEQ ID NO:1916, SEQ ID NO:1917, SEQ ID NO:1918, SEQ ID NO:1919, SEQ ID NO:1920, SEQ ID NO:1957, SEQ ID NO:1958, SEQ ID NO:1959, SEQ ID NO:1960, SEQ ID NO:1961, SEQ ID NO:1962, SEQ ID NO:1963, SEQ ID NO:1964, SEQ ID NO:1965, SEQ ID NO:1966, SEQ ID NO:1967, SEQ ID NO:1968, SEQ ID NO:1969, SEQ ID NO:1970, SEQ ID NO:1971, SEQ ID NO:1972, SEQ ID NO:1973, SEQ ID NO: No. 1974, No. 1975, No. 1976, No. 1977, No. 1978, No. 1979, No. 1980, No. 1981, No. 1982, No. 1983, No. 1984, No. 1985, No. 1986, No. 1987, No. 1988, No. 1989, No. 1990, No. 1991, No. 1992, No. 1993, No. 1994, No. 1995, No. 1996, No. 1997, No. 1998, No. 1999, No. 2000, No. 2001,SEQ ID NO:2002, SEQ ID NO:2003, SEQ ID NO:2004, SEQ ID NO:2005, SEQ ID NO:2006, SEQ ID NO:2007, SEQ ID NO:2008, SEQ ID NO:2009, SEQ ID NO:2010, SEQ ID NO:2011, SEQ ID NO:2012, SEQ ID NO:2013, SEQ ID NO:2014, SEQ ID NO:2015, SEQ ID NO:2016, SEQ ID NO:2017, SEQ ID NO:2018, SEQ ID NO:2019, SEQ ID NO:2020, SEQ ID NO:2021, SEQ ID NO:2022, SEQ ID NO:2023, SEQ ID NO:2024, SEQ ID NO:2025, SEQ ID NO:2026, SEQ ID NO:2027, SEQ ID NO:2028, 29, SEQ ID NO:2030, SEQ ID NO:2031, SEQ ID NO:2032, SEQ ID NO:2033, SEQ ID NO:2034, SEQ ID NO:2035, SEQ ID NO:2036, SEQ ID NO:2037, SEQ ID NO:2038, SEQ ID NO:2039, SEQ ID NO:2040, SEQ ID NO:2041, SEQ ID NO:2042, SEQ ID NO:2043, SEQ ID NO:2044, SEQ ID NO:2045, SEQ ID NO:2046, SEQ ID NO:2047, SEQ ID NO:2048, SEQ ID NO:2049, SEQ ID NO:2050, SEQ ID NO:2051, SEQ ID NO:2052, SEQ ID NO:2053, SEQ ID NO:2054, SEQ ID NO:2055, SEQ ID NO:2056, 2057, SEQ ID NO:2058, SEQ ID NO:2059, SEQ ID NO:2060, SEQ ID NO:2061, SEQ ID NO:2062, SEQ ID NO:2063, SEQ ID NO:2064, SEQ ID NO:2065, SEQ ID NO:2066, SEQ ID NO:2067, SEQ ID NO:2068, SEQ ID NO:2069, SEQ ID NO:2070, SEQ ID NO:2071, SEQ ID NO:2072, SEQ ID NO:2073, SEQ ID NO:2074, SEQ ID NO:2075, SEQ ID NO:2076, SEQ ID NO:2077, SEQ ID NO:2078, SEQ ID NO:2079, SEQ ID NO:2080, SEQ ID NO:2081, SEQ ID NO:2082, SEQ ID NO:2083, SEQ ID NO:2084, SEQ ID NO: No. 2085, No. 2086, No. 2087, No. 2088, No. 2089, No. 2090, No. 2091, No. 2092, No. 2093, No. 2094, No. 2095, No. 2096, No. 2097, No. 2098, No. 2099, No. 2100, No. 2101, No. 2102, No. 2103, No. 2104, No. 2105, No. 2106, No. 2107, No. 2108, No. 2109, No. 2110, No. 2111, No. 2112,SEQ ID NO:2113, SEQ ID NO:2114, SEQ ID NO:2115, SEQ ID NO:2116, SEQ ID NO:2117, SEQ ID NO:2118, SEQ ID NO:2119, SEQ ID NO:2120, SEQ ID NO:2121, SEQ ID NO:2122, SEQ ID NO:2123, SEQ ID NO:2124, SEQ ID NO:2125, SEQ ID NO:2126, SEQ ID NO:2127, SEQ ID NO:2128, SEQ ID NO:2129, SEQ ID NO:2130, SEQ ID NO:2131, SEQ ID NO:2132, SEQ ID NO:2133, SEQ ID NO:2134, SEQ ID NO:2135, SEQ ID NO:2136, SEQ ID NO:2137, SEQ ID NO:2138, SEQ ID NO:2139, SEQ ID NO:2140, SEQ ID NO:2141, SEQ ID NO:2142, SEQ ID NO:2143, SEQ ID NO:2144, SEQ ID NO:2145, SEQ ID NO:2146, SEQ ID NO:2147, SEQ ID NO:2148, 49, SEQ ID NO:2150, SEQ ID NO:2151, SEQ ID NO:2152, SEQ ID NO:2153, SEQ ID NO:2154, SEQ ID NO:2155, SEQ ID NO:2156, SEQ ID NO:2157, SEQ ID NO:2158, SEQ ID NO:2159, SEQ ID NO:2160, SEQ ID NO:2161, SEQ ID NO:2162, SEQ ID NO:2163, SEQ ID NO:2164, SEQ ID NO:2165, SEQ ID NO:2166, SEQ ID NO:2167, SEQ ID NO:2168, SEQ ID NO:2169, SEQ ID NO:2170, SEQ ID NO:2171, 2172, SEQ ID NO:2173, SEQ ID NO:2174, SEQ ID NO:2175, SEQ ID NO:2176, SEQ ID NO:2177, SEQ ID NO:2178, SEQ ID NO:2179, SEQ ID NO:2180, or SEQ ID NO:2181; (b) is a synthetic sequence of (a) with codons optimized for heterologous expression; or (c) encodes at least one CGI factor motif. The nucleotide sequence encoding at least one CGI factor of the preceding embodiment is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22,SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, No. 58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125 , SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137, SEQ ID NO:138, SEQ ID NO:139, SEQ ID NO:140, SEQ ID NO:141, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO:144, SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:147, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:150, SEQ ID NO:151, SEQ ID NO:152, SEQ ID NO:153, SEQ ID NO:154, SEQ ID NO:155, SEQ ID NO:156,SEQ ID NO:157, SEQ ID NO:158, SEQ ID NO:159, SEQ ID NO:160, SEQ ID NO:161, SEQ ID NO:162, SEQ ID NO:163, SEQ ID NO:164, SEQ ID NO:165, SEQ ID NO:166, SEQ ID NO:167, SEQ ID NO:168, SEQ ID NO:169, SEQ ID NO:170, SEQ ID NO:171, SEQ ID NO:172, SEQ ID NO:173, SEQ ID NO:174, SEQ ID NO:175, SEQ ID NO:176, SEQ ID NO:177, SEQ ID NO:178, SEQ ID NO:179, SEQ ID NO:180, SEQ ID NO:181, SEQ ID NO:182, SEQ ID NO:183, SEQ ID NO:184, SEQ ID NO:185, SEQ ID NO:186, SEQ ID NO:187, No. 188, SEQ ID NO. 189, SEQ ID NO. 190, SEQ ID NO. 191, SEQ ID NO. 192, SEQ ID NO. 193, SEQ ID NO. 194, SEQ ID NO. 195, SEQ ID NO. 196, SEQ ID NO. 197, SEQ ID NO. 198, SEQ ID NO. 199, SEQ ID NO. 200, SEQ ID NO. 201, SEQ ID NO. 202, SEQ ID NO. 203, SEQ ID NO. 204, SEQ ID NO. 205, SEQ ID NO. 206, SEQ ID NO. 207, SEQ ID NO. 208, SEQ ID NO. 209, SEQ ID NO. 210, SEQ ID NO. 211, SEQ ID NO. 212, SEQ ID NO. 213, SEQ ID NO. 214, SEQ ID NO. 215, SEQ ID NO. 216, SEQ ID NO. 217, SEQ ID NO. 218, 219, SEQ ID NO:220, SEQ ID NO:221, SEQ ID NO:222, SEQ ID NO:223, SEQ ID NO:224, SEQ ID NO:225, SEQ ID NO:226, SEQ ID NO:227, SEQ ID NO:228, SEQ ID NO:229, SEQ ID NO:230, SEQ ID NO:231, SEQ ID NO:232, SEQ ID NO:233, SEQ ID NO:234, SEQ ID NO:235, SEQ ID NO:236, SEQ ID NO:237, SEQ ID NO:238, SEQ ID NO:239, SEQ ID NO:240, SEQ ID NO:241, SEQ ID NO:242, SEQ ID NO:243, SEQ ID NO:244, SEQ ID NO:245, SEQ ID NO:246, SEQ ID NO:247, SEQ ID NO:248, SEQ ID NO:249, SEQ ID NO:25 0, SEQ ID NO:251, SEQ ID NO:252, SEQ ID NO:253, SEQ ID NO:254, SEQ ID NO:255, SEQ ID NO:256, SEQ ID NO:257, SEQ ID NO:258, SEQ ID NO:259, SEQ ID NO:260, SEQ ID NO:261, SEQ ID NO:262, SEQ ID NO:263, SEQ ID NO:264, SEQ ID NO:265, SEQ ID NO:266, SEQ ID NO:267, SEQ ID NO:268, SEQ ID NO:269, SEQ ID NO:270, SEQ ID NO:271, SEQ ID NO:272, SEQ ID NO:273, SEQ ID NO:274, SEQ ID NO:275, SEQ ID NO:276, SEQ ID NO:277, SEQ ID NO:278, SEQ ID NO:279, SEQ ID NO:280, SEQ ID NO:281,SEQ ID NO:282, SEQ ID NO:283, SEQ ID NO:284, SEQ ID NO:285, SEQ ID NO:286, SEQ ID NO:287, SEQ ID NO:288, SEQ ID NO:289, SEQ ID NO:290, SEQ ID NO:291, SEQ ID NO:292, SEQ ID NO:293, SEQ ID NO:294, SEQ ID NO:295, SEQ ID NO:296, SEQ ID NO:297, SEQ ID NO:298, SEQ ID NO:299, SEQ ID NO:300, SEQ ID NO:301, SEQ ID NO:302, SEQ ID NO:303, SEQ ID NO:304, SEQ ID NO:305, SEQ ID NO:306, SEQ ID NO:307, SEQ ID NO:308, SEQ ID NO:309, SEQ ID NO:310, SEQ ID NO:311, SEQ ID NO:312, SEQ ID NO: No. 313, SEQ ID NO. 314, SEQ ID NO. 315, SEQ ID NO. 316, SEQ ID NO. 317, SEQ ID NO. 318, SEQ ID NO. 319, SEQ ID NO. 320, SEQ ID NO. 321, SEQ ID NO. 322, SEQ ID NO. 323, SEQ ID NO. 324, SEQ ID NO. 325, SEQ ID NO. 326, SEQ ID NO. 327, SEQ ID NO. 328, SEQ ID NO. 329, SEQ ID NO. 330, SEQ ID NO. 331, SEQ ID NO. 332, SEQ ID NO. 333, SEQ ID NO. 334, SEQ ID NO. 335, SEQ ID NO. 336, SEQ ID NO. 337, SEQ ID NO. 338, SEQ ID NO. 339, SEQ ID NO. 340, SEQ ID NO. 341, SEQ ID NO. 342, SEQ ID NO. 343, 344, SEQ ID NO:345, SEQ ID NO:346, SEQ ID NO:347, SEQ ID NO:348, SEQ ID NO:349, SEQ ID NO:350, SEQ ID NO:351, SEQ ID NO:352, SEQ ID NO:353, SEQ ID NO:354, SEQ ID NO:355, SEQ ID NO:356, SEQ ID NO:357, SEQ ID NO:358, SEQ ID NO:359, SEQ ID NO:360, SEQ ID NO:361, SEQ ID NO:362, SEQ ID NO:363, SEQ ID NO:364, SEQ ID NO:365, SEQ ID NO:366, SEQ ID NO:367, SEQ ID NO:368, SEQ ID NO:369, SEQ ID NO:370, SEQ ID NO:371, SEQ ID NO:372, SEQ ID NO:373, SEQ ID NO:374, SEQ ID NO:375 5, SEQ ID NO:376, SEQ ID NO:377, SEQ ID NO:378, SEQ ID NO:379, SEQ ID NO:380, SEQ ID NO:381, SEQ ID NO:382, SEQ ID NO:383, SEQ ID NO:384, SEQ ID NO:385, SEQ ID NO:386, SEQ ID NO:387, SEQ ID NO:388, SEQ ID NO:389, SEQ ID NO:390, SEQ ID NO:391, SEQ ID NO:392, SEQ ID NO:393, SEQ ID NO:394, SEQ ID NO:395, SEQ ID NO:396, SEQ ID NO:397, SEQ ID NO:398, SEQ ID NO:399, SEQ ID NO:400, SEQ ID NO:401, SEQ ID NO:402, SEQ ID NO:403, SEQ ID NO:404, SEQ ID NO:405, SEQ ID NO:406,SEQ ID NO:407, SEQ ID NO:408, SEQ ID NO:409, SEQ ID NO:410, SEQ ID NO:411, SEQ ID NO:412, SEQ ID NO:413, SEQ ID NO:414, SEQ ID NO:415, SEQ ID NO:416, SEQ ID NO:417, SEQ ID NO:418, SEQ ID NO:419, SEQ ID NO:420, SEQ ID NO:421, SEQ ID NO:422, SEQ ID NO:423, SEQ ID NO:424, SEQ ID NO:425, SEQ ID NO:426, SEQ ID NO:427, SEQ ID NO:428, SEQ ID NO:429, SEQ ID NO:430, SEQ ID NO:431, SEQ ID NO:432, SEQ ID NO:433, SEQ ID NO:434, SEQ ID NO:435, SEQ ID NO:436, SEQ ID NO:437, SEQ ID NO: No. 438, SEQ ID NO. 439, SEQ ID NO. 440, SEQ ID NO. 441, SEQ ID NO. 442, SEQ ID NO. 443, SEQ ID NO. 444, SEQ ID NO. 445, SEQ ID NO. 446, SEQ ID NO. 447, SEQ ID NO. 448, SEQ ID NO. 449, SEQ ID NO. 450, SEQ ID NO. 451, SEQ ID NO. 452, SEQ ID NO. 453, SEQ ID NO. 454, SEQ ID NO. 455, SEQ ID NO. 456, SEQ ID NO. 457, SEQ ID NO. 458, SEQ ID NO. 459, SEQ ID NO. 460, SEQ ID NO. 461, SEQ ID NO. 462, SEQ ID NO. 463, SEQ ID NO. 464, SEQ ID NO. 465, SEQ ID NO. 466, SEQ ID NO. 467, SEQ ID NO. 468, 469, SEQ ID NO:470, SEQ ID NO:471, SEQ ID NO:472, SEQ ID NO:473, SEQ ID NO:474, SEQ ID NO:475, SEQ ID NO:476, SEQ ID NO:477, SEQ ID NO:478, SEQ ID NO:479, SEQ ID NO:480, SEQ ID NO:481, SEQ ID NO:482, SEQ ID NO:483, SEQ ID NO:484, SEQ ID NO:485, SEQ ID NO:486, SEQ ID NO:487, SEQ ID NO:488, SEQ ID NO:489, SEQ ID NO:490, SEQ ID NO:491, SEQ ID NO:492, SEQ ID NO:493, SEQ ID NO:494, SEQ ID NO:495, SEQ ID NO:496, SEQ ID NO:497, SEQ ID NO:498, SEQ ID NO:499, SEQ ID NO:50 0, SEQ ID NO:501, SEQ ID NO:502, SEQ ID NO:503, SEQ ID NO:504, SEQ ID NO:505, SEQ ID NO:506, SEQ ID NO:507, SEQ ID NO:508, SEQ ID NO:509, SEQ ID NO:510, SEQ ID NO:511, SEQ ID NO:512, SEQ ID NO:513, SEQ ID NO:514, SEQ ID NO:515, SEQ ID NO:516, SEQ ID NO:517, SEQ ID NO:518, SEQ ID NO:519, SEQ ID NO:520, SEQ ID NO:521, SEQ ID NO:522, SEQ ID NO:523, SEQ ID NO:524, SEQ ID NO:525, SEQ ID NO:526, SEQ ID NO:527, SEQ ID NO:528, SEQ ID NO:529, SEQ ID NO:530, SEQ ID NO:531,SEQ ID NO:532, SEQ ID NO:533, SEQ ID NO:534, SEQ ID NO:535, SEQ ID NO:536, SEQ ID NO:537, SEQ ID NO:538, SEQ ID NO:539, SEQ ID NO:540, SEQ ID NO:541, SEQ ID NO:542, SEQ ID NO:543, SEQ ID NO:544, SEQ ID NO:545, SEQ ID NO:546, SEQ ID NO:5, 47, SEQ ID NO:548, SEQ ID NO:549, SEQ ID NO:550, SEQ ID NO:551, SEQ ID NO:552, SEQ ID NO:553, SEQ ID NO:554, SEQ ID NO:555, SEQ ID NO:556, SEQ ID NO:557, SEQ ID NO:558, SEQ ID NO:559, SEQ ID NO:560, SEQ ID NO:561, SEQ ID NO:562, SEQ ID NO:563, SEQ ID NO:564, SEQ ID NO:565, SEQ ID NO:566, SEQ ID NO:567, SEQ ID NO:568, SEQ ID NO:569, SEQ ID NO:570, SEQ ID NO:571, SEQ ID NO:572, SEQ ID NO:573, SEQ ID NO:574, SEQ ID NO:575, SEQ ID NO:576, SEQ ID NO:577, 78, SEQ ID NO:579, SEQ ID NO:580, SEQ ID NO:581, SEQ ID NO:582, SEQ ID NO:583, SEQ ID NO:584, SEQ ID NO:585, SEQ ID NO:586, SEQ ID NO:587, SEQ ID NO:588, SEQ ID NO:589, SEQ ID NO:590, SEQ ID NO:591, SEQ ID NO:592, SEQ ID NO:593, SEQ ID NO:594, SEQ ID NO:595, SEQ ID NO:596, SEQ ID NO:597, SEQ ID NO:598, SEQ ID NO:599, SEQ ID NO:600, SEQ ID NO:601, SEQ ID NO:602, SEQ ID NO:603, SEQ ID NO:604, SEQ ID NO:605, SEQ ID NO:606, SEQ ID NO:607, SEQ ID NO:608, SEQ ID NO:60 9, SEQ ID NO:610, SEQ ID NO:611, SEQ ID NO:612, SEQ ID NO:613, SEQ ID NO:614, SEQ ID NO:615, SEQ ID NO:616, SEQ ID NO:617, SEQ ID NO:618, SEQ ID NO:619, SEQ ID NO:620, SEQ ID NO:621, SEQ ID NO:622, SEQ ID NO:623, SEQ ID NO:624, SEQ ID NO:625, SEQ ID NO:626, SEQ ID NO:627, SEQ ID NO:628, SEQ ID NO:629, SEQ ID NO:630, SEQ ID NO:631, SEQ ID NO:632, SEQ ID NO:633, SEQ ID NO:634, SEQ ID NO:635, SEQ ID NO:636, SEQ ID NO:637, SEQ ID NO:638, SEQ ID NO:639, SEQ ID NO:640 , SEQ ID NO:641, SEQ ID NO:642, SEQ ID NO:643, SEQ ID NO:644, SEQ ID NO:645, SEQ ID NO:646, SEQ ID NO:647, SEQ ID NO:648, SEQ ID NO:649, SEQ ID NO:650, SEQ ID NO:651, SEQ ID NO:652, SEQ ID NO:653, SEQ ID NO:654, SEQ ID NO:655, SEQ ID NO:656, SEQ ID NO:657, SEQ ID NO:658, SEQ ID NO:659, SEQ ID NO:660, SEQ ID NO:661, SEQ ID NO:662, SEQ ID NO:663, SEQ ID NO:664, SEQ ID NO:665, SEQ ID NO:666, SEQ ID NO:667, SEQ ID NO:668, SEQ ID NO:669, SEQ ID NO:670, SEQ ID NO:671,SEQ ID NO:672, SEQ ID NO:673, SEQ ID NO:674, SEQ ID NO:675, SEQ ID NO:676, SEQ ID NO:677, SEQ ID NO:678, SEQ ID NO:679, SEQ ID NO:680, SEQ ID NO:681, SEQ ID NO:682, SEQ ID NO:683, SEQ ID NO:684, SEQ ID NO:685, SEQ ID NO:686, SEQ ID NO:687, SEQ ID NO:688, SEQ ID NO:689, SEQ ID NO:690, SEQ ID NO:691, SEQ ID NO:692, SEQ ID NO:693, SEQ ID NO:694, SEQ ID NO:695, SEQ ID NO:696, SEQ ID NO:697, SEQ ID NO:698, SEQ ID NO:699, SEQ ID NO:700, SEQ ID NO:701, SEQ ID NO:702, SEQ ID NO: No. 703, SEQ ID NO: 704, SEQ ID NO: 705, SEQ ID NO: 706, SEQ ID NO: 707, SEQ ID NO: 708, SEQ ID NO: 709, SEQ ID NO: 710, SEQ ID NO: 711, SEQ ID NO: 712, SEQ ID NO: 713, SEQ ID NO: 714, SEQ ID NO: 715, SEQ ID NO: 716, SEQ ID NO: 717, SEQ ID NO: 718, SEQ ID NO: 719, SEQ ID NO: 720, SEQ ID NO: 721, SEQ ID NO: 722, SEQ ID NO: 723, SEQ ID NO: 724, SEQ ID NO: 725, SEQ ID NO: 726, SEQ ID NO: 727, SEQ ID NO: 728, SEQ ID NO: 729, SEQ ID NO: 730, SEQ ID NO: 731, SEQ ID NO: 732, SEQ ID NO: 733, 734, SEQ ID NO:735, SEQ ID NO:736, SEQ ID NO:737, SEQ ID NO:738, SEQ ID NO:739, SEQ ID NO:740, SEQ ID NO:741, SEQ ID NO:742, SEQ ID NO:743, SEQ ID NO:744, SEQ ID NO:745, SEQ ID NO:746, SEQ ID NO:747, SEQ ID NO:748, SEQ ID NO:749, SEQ ID NO:750, SEQ ID NO:751, SEQ ID NO:752, SEQ ID NO:753, SEQ ID NO:754, SEQ ID NO:755, SEQ ID NO:756, SEQ ID NO:757, SEQ ID NO:758, SEQ ID NO:759, SEQ ID NO:760, SEQ ID NO:761, SEQ ID NO:762, SEQ ID NO:763, SEQ ID NO:764, SEQ ID NO:76 5, SEQ ID NO:766, SEQ ID NO:767, SEQ ID NO:768, SEQ ID NO:769, SEQ ID NO:770, SEQ ID NO:771, SEQ ID NO:772, SEQ ID NO:773, SEQ ID NO:774, SEQ ID NO:775, SEQ ID NO:776, SEQ ID NO:777, SEQ ID NO:778, SEQ ID NO:779, SEQ ID NO:780, SEQ ID NO:781, SEQ ID NO:782, SEQ ID NO:783, SEQ ID NO:784, SEQ ID NO:785, SEQ ID NO:786, SEQ ID NO:787, SEQ ID NO:788, SEQ ID NO:789, SEQ ID NO:790, SEQ ID NO:791, SEQ ID NO:792, SEQ ID NO:793, SEQ ID NO:794, SEQ ID NO:795, SEQ ID NO:796,SEQ ID NO:797, SEQ ID NO:798, SEQ ID NO:799, SEQ ID NO:800, SEQ ID NO:801, SEQ ID NO:802, SEQ ID NO:803, SEQ ID NO:804, SEQ ID NO:805, SEQ ID NO:806, SEQ ID NO:807, SEQ ID NO:808, SEQ ID NO:809, SEQ ID NO:810, SEQ ID NO:811, SEQ ID NO:812, SEQ ID NO:813, SEQ ID NO:814, SEQ ID NO:815, SEQ ID NO:816, SEQ ID NO:817, SEQ ID NO:818, SEQ ID NO:819, SEQ ID NO:820, SEQ ID NO:821, SEQ ID NO:822, SEQ ID NO:823, SEQ ID NO:824, SEQ ID NO:825, SEQ ID NO:826, SEQ ID NO:827, No. 828, SEQ ID NO: 829, SEQ ID NO: 830, SEQ ID NO: 831, SEQ ID NO: 832, SEQ ID NO: 833, SEQ ID NO: 834, SEQ ID NO: 835, SEQ ID NO: 836, SEQ ID NO: 837, SEQ ID NO: 838, SEQ ID NO: 839, SEQ ID NO: 840, SEQ ID NO: 841, SEQ ID NO: 842, SEQ ID NO: 843, SEQ ID NO: 844, SEQ ID NO: 845, SEQ ID NO: 846, SEQ ID NO: 847, SEQ ID NO: 848, SEQ ID NO: 849, SEQ ID NO: 850, SEQ ID NO: 851, SEQ ID NO: 852, SEQ ID NO: 853, SEQ ID NO: 854, SEQ ID NO: 855, SEQ ID NO: 856, SEQ ID NO: 857, SEQ ID NO: 858, 859, SEQ ID NO:860, SEQ ID NO:861, SEQ ID NO:862, SEQ ID NO:863, SEQ ID NO:864, SEQ ID NO:865, SEQ ID NO:866, SEQ ID NO:867, SEQ ID NO:868, SEQ ID NO:869, SEQ ID NO:870, SEQ ID NO:871, SEQ ID NO:872, SEQ ID NO:873, SEQ ID NO:874, SEQ ID NO:875, SEQ ID NO:876, SEQ ID NO:877, SEQ ID NO:878, SEQ ID NO:879, SEQ ID NO:880, SEQ ID NO:881, SEQ ID NO:882, SEQ ID NO:883, SEQ ID NO:884, SEQ ID NO:885, SEQ ID NO:886, SEQ ID NO:887, SEQ ID NO:888, SEQ ID NO:889, SEQ ID NO:89 0, SEQ ID NO:891, SEQ ID NO:892, SEQ ID NO:893, SEQ ID NO:894, SEQ ID NO:895, SEQ ID NO:896, SEQ ID NO:897, SEQ ID NO:898, SEQ ID NO:899, SEQ ID NO:900, SEQ ID NO:901, SEQ ID NO:902, SEQ ID NO:903, SEQ ID NO:904, SEQ ID NO:905, SEQ ID NO:906, SEQ ID NO:907, SEQ ID NO:908, SEQ ID NO:909, SEQ ID NO:910, SEQ ID NO:911, SEQ ID NO:912, SEQ ID NO:913, SEQ ID NO:914, SEQ ID NO:915, SEQ ID NO:916, SEQ ID NO:917, SEQ ID NO:918, SEQ ID NO:919, SEQ ID NO:920, SEQ ID NO:921,SEQ ID NO: 922, SEQ ID NO: 923, SEQ ID NO: 924, SEQ ID NO: 925, SEQ ID NO: 926, SEQ ID NO: 927, SEQ ID NO: 928, SEQ ID NO: 929, SEQ ID NO: 930, SEQ ID NO: 931, SEQ ID NO: 932, SEQ ID NO: 933, SEQ ID NO: 934, SEQ ID NO: 935, SEQ ID NO: 936, SEQ ID NO: 937, SEQ ID NO: 938, SEQ ID NO: 939, SEQ ID NO: 940, SEQ ID NO: 941, SEQ ID NO: 942, SEQ ID NO: 943, SEQ ID NO: 944, SEQ ID NO: 945, SEQ ID NO: 946, SEQ ID NO: 947, SEQ ID NO: 948, SEQ ID NO: 949, SEQ ID NO: 950, SEQ ID NO: 951, SEQ ID NO: 952, SEQ ID NO: 953, SEQ ID NO: 954, SEQ ID NO: 955, SEQ ID NO: 956, SEQ ID NO: 957, SEQ ID NO: 958, SEQ ID NO: 959, SEQ ID NO: 960, or SEQ ID NOs: 3362 to 5698. In additional embodiments of this aspect, the CGI factor is selected from the group consisting of SEQ ID NO:2182, SEQ ID NO:2183, SEQ ID NO:2184, SEQ ID NO:2185, SEQ ID NO:2186, SEQ ID NO:2187, SEQ ID NO:2188, SEQ ID NO:2189, SEQ ID NO:2194, SEQ ID NO:2195, SEQ ID NO:2196, SEQ ID NO:2197, SEQ ID NO:2198, SEQ ID NO:2199, SEQ ID NO:2200, SEQ ID NO:2201, SEQ ID NO:2202, SEQ ID NO:2203, SEQ ID NO:2204, SEQ ID NO:2205, SEQ ID NO:2206, SEQ ID NO:2207, SEQ ID NO:2208, SEQ ID NO:2209, SEQ ID NO:2210, SEQ ID NO:2215, The sequence may include sequence number 2216, SEQ ID NO:2217, SEQ ID NO:2218, SEQ ID NO:2219, SEQ ID NO:2220, SEQ ID NO:2221, SEQ ID NO:2222, SEQ ID NO:2223, SEQ ID NO:2224, SEQ ID NO:2225, SEQ ID NO:2226, SEQ ID NO:2227, SEQ ID NO:2228, SEQ ID NO:2229, SEQ ID NO:2230, SEQ ID NO:2231, SEQ ID NO:2232, SEQ ID NO:2233, SEQ ID NO:2234, SEQ ID NO:2235, SEQ ID NO:2236, SEQ ID NO:2237, SEQ ID NO:2238, SEQ ID NO:2239, SEQ ID NO:2240, SEQ ID NO:2241, SEQ ID NO:2242, or SEQ ID NO:2243. In some embodiments of this aspect, the CGI factor motif is SEQ ID NO:1921, SEQ ID NO:1922, SEQ ID NO:1923, SEQ ID NO:1924, SEQ ID NO:1925, SEQ ID NO:1926, SEQ ID NO:1927, SEQ ID NO:1928, SEQ ID NO:1929, SEQ ID NO:1930, SEQ ID NO:1931, SEQ ID NO:1932, SEQ ID NO:1933,At least one of SEQ ID NO:1934, SEQ ID NO:1935, SEQ ID NO:1936, SEQ ID NO:1937, SEQ ID NO:1938, SEQ ID NO:1939, SEQ ID NO:1940, SEQ ID NO:1941, SEQ ID NO:1942, SEQ ID NO:1943, SEQ ID NO:1944, SEQ ID NO:1945, SEQ ID NO:1946, SEQ ID NO:1947, SEQ ID NO:1948, SEQ ID NO:1949, SEQ ID NO:1950, SEQ ID NO:1951, SEQ ID NO:1952, SEQ ID NO:1953, SEQ ID NO:1954, SEQ ID NO:1955, or SEQ ID NO:1956. In still further embodiments of this aspect, the CGI factor is SEQ ID NO:2457, SEQ ID NO:2458, SEQ ID NO:2459, SEQ ID NO:2460, SEQ ID NO:2461, SEQ ID NO:2462, SEQ ID NO:2463, SEQ ID NO:2464, SEQ ID NO:2465, SEQ ID NO:2466, SEQ ID NO:2467, SEQ ID NO:2468, SEQ ID NO:2469, SEQ ID NO:2470, SEQ ID NO:2471, SEQ ID NO:2472, SEQ ID NO:2473, SEQ ID NO:2474, SEQ ID NO:2475, SEQ ID NO:2476, SEQ ID NO:2477, SEQ ID NO:2478, SEQ ID NO:2479, SEQ ID NO:2480, SEQ ID NO:2481, SEQ ID NO:2482, SEQ ID NO:2483, SEQ ID NO:2484, SEQ ID NO:2485, 75, SEQ ID NO:2476, SEQ ID NO:2477, SEQ ID NO:2478, SEQ ID NO:2479, SEQ ID NO:2480, SEQ ID NO:2481, SEQ ID NO:2482, SEQ ID NO:2483, SEQ ID NO:2484, SEQ ID NO:2485, SEQ ID NO:2486, SEQ ID NO:2487, SEQ ID NO:2488, SEQ ID NO:2489, SEQ ID NO:2490, SEQ ID NO:2491, SEQ ID NO:2492, SEQ ID NO:2493, SEQ ID NO:2494, SEQ ID NO:2495, SEQ ID NO:2496, Column number 2497, sequence number 2498, sequence number 2499, sequence number 2500, sequence number 2501, sequence number 2502, sequence number 2503, sequence number 2504, sequence number 2505, sequence number 2506, sequence number 2507, sequence number 2508, sequence number 2509, sequence number 2510, sequence number 2511, sequence number 2512, sequence number 2513, sequence number 2514, sequence number 2515, sequence number 2516, sequence number 2517, sequence number 2 518, SEQ ID NO:2519, SEQ ID NO:2520, SEQ ID NO:2521, SEQ ID NO:2522, SEQ ID NO:2523, SEQ ID NO:2524, SEQ ID NO:2525, SEQ ID NO:2526, SEQ ID NO:2527, SEQ ID NO:2528, SEQ ID NO:2529, SEQ ID NO:2530, SEQ ID NO:2531, SEQ ID NO:2532, SEQ ID NO:2533, SEQ ID NO:2534, SEQ ID NO:2535, SEQ ID NO:2536, SEQ ID NO:2537, SEQ ID NO:2538, SEQ ID NO:2539,SEQ ID NO:2540, SEQ ID NO:2541, SEQ ID NO:2542, SEQ ID NO:2543, SEQ ID NO:2544, SEQ ID NO:2545, SEQ ID NO:2546, SEQ ID NO:2547, SEQ ID NO:2548, SEQ ID NO:2549, SEQ ID NO:2550, SEQ ID NO:2551, SEQ ID NO:2552, SEQ ID NO:2553, SEQ ID NO:2554, SEQ ID NO: 2555, SEQ ID NO:2556, SEQ ID NO:2557, SEQ ID NO:2558, SEQ ID NO:2559, SEQ ID NO:2560, SEQ ID NO:2561, SEQ ID NO:2562, SEQ ID NO:2563, SEQ ID NO:2564, SEQ ID NO:2565, SEQ ID NO:2566, SEQ ID NO:2567, SEQ ID NO:2568, SEQ ID NO:2569, SEQ ID NO:2570, SEQ ID NO:2571, SEQ ID NO:2572, SEQ ID NO:2573, SEQ ID NO:2574, SEQ ID NO:2575, SEQ ID NO:2576, SEQ ID NO:2577, SEQ ID NO:2578, SEQ ID NO:2579, SEQ ID NO:2580, SEQ ID NO:2581, SEQ ID NO:2582, SEQ ID NO:2583, SEQ ID NO:2584, SEQ ID NO:2585, SEQ ID NO:2586, SEQ ID NO:2587, SEQ ID NO:2588, SEQ ID NO:2589, SEQ ID NO:2590, SEQ ID NO:2591, SEQ ID NO:2592, SEQ ID NO:2593, SEQ ID NO:2594, SEQ ID NO:2595, SEQ ID NO:2596, SEQ ID NO:2597, SEQ ID NO:2598, SEQ ID NO:2599, SEQ ID NO:2600, SEQ ID NO:2601, SEQ ID NO:2602, SEQ ID NO:2603, SEQ ID NO:2604, SEQ ID NO:2605, SEQ ID NO:2606, SEQ ID NO:2607, SEQ ID NO:2608, SEQ ID NO:2609, SEQ ID NO:26 10, SEQ ID NO:2611, SEQ ID NO:2612, SEQ ID NO:2613, SEQ ID NO:2614, SEQ ID NO:2615, SEQ ID NO:2616, SEQ ID NO:2617, SEQ ID NO:2618, SEQ ID NO:2619, SEQ ID NO:2620, SEQ ID NO:2621, SEQ ID NO:2622, SEQ ID NO:2623, SEQ ID NO:2624, SEQ ID NO:2625, SEQ ID NO:2626, SEQ ID NO:2627, SEQ ID NO:2628, SEQ ID NO:2629, SEQ ID NO:2630, SEQ ID NO:2631, SEQ ID NO:2632, SEQ ID NO:2633, SEQ ID NO:2634, SEQ ID NO:2635, SEQ ID NO:2636, SEQ ID NO:2637, SEQ ID NO: No. 2638, No. 2639, No. 2640, No. 2641, No. 2642, No. 2643, No. 2644, No. 2645, No. 2646, No. 2647, No. 2648, No. 2649, No. 2650, No. 2651, No. 2652, No. 2653, No. 2654, No. 2655, No. 2656, No. 2657, No. 2658, No. 2659, No. 2660, No. 2661, No. 2662, No. 2663, No. 2664, No. 2665,SEQ ID NO:2666, SEQ ID NO:2667, SEQ ID NO:2668, SEQ ID NO:2669, SEQ ID NO:2670, SEQ ID NO:2671, SEQ ID NO:2672, SEQ ID NO:2673, SEQ ID NO:2674, SEQ ID NO:2675, SEQ ID NO:2676, SEQ ID NO:2677, SEQ ID NO:2678, SEQ ID NO:2679, SEQ ID NO:2680, SEQ ID NO:2681, SEQ ID NO:2682, SEQ ID NO:2683, SEQ ID NO:2684, SEQ ID NO:2685, SEQ ID NO:2686, SEQ ID NO:2687, SEQ ID NO:2688, SEQ ID NO:2689, SEQ ID NO:2690, SEQ ID NO:2691, SEQ ID NO:2692, SEQ ID NO:26 93, SEQ ID NO:2694, SEQ ID NO:2695, SEQ ID NO:2696, SEQ ID NO:2697, SEQ ID NO:2698, SEQ ID NO:2699, SEQ ID NO:2700, SEQ ID NO:2701, SEQ ID NO:2702, SEQ ID NO:2703, SEQ ID NO:2704, SEQ ID NO:2705, SEQ ID NO:2706, SEQ ID NO:2707, SEQ ID NO:2708, SEQ ID NO:2709, SEQ ID NO:2710, SEQ ID NO:2711, SEQ ID NO:2712, SEQ ID NO:2713, SEQ ID NO:2714, SEQ ID NO:2715, SEQ ID NO:2716, SEQ ID NO:2717, SEQ ID NO:2718, SEQ ID NO:2719, SEQ ID NO:2720, 2721, SEQ ID NO:2722, SEQ ID NO:2723, SEQ ID NO:2724, SEQ ID NO:2725, SEQ ID NO:2726, SEQ ID NO:2727, SEQ ID NO:2728, SEQ ID NO:2729, SEQ ID NO:2730, SEQ ID NO:2731, SEQ ID NO:2732, SEQ ID NO:2733, SEQ ID NO:2734, SEQ ID NO:2735, SEQ ID NO:2736, SEQ ID NO:2737, SEQ ID NO:2738, SEQ ID NO:2739, SEQ ID NO:2740, SEQ ID NO:2741, SEQ ID NO:2742, SEQ ID NO:2743, SEQ ID NO:2744, SEQ ID NO:2745, SEQ ID NO:2746, SEQ ID NO:2747, SEQ ID NO:2748, SEQ ID NO: No. 2749, SEQ ID NO. 2750, SEQ ID NO. 2751, SEQ ID NO. 2752, SEQ ID NO. 2753, SEQ ID NO. 2754, SEQ ID NO. 2755, SEQ ID NO. 2756, SEQ ID NO. 2757, SEQ ID NO. 2758, SEQ ID NO. 2759, SEQ ID NO. 2760, SEQ ID NO. 2761, SEQ ID NO. 2762, SEQ ID NO. 2763, SEQ ID NO. 2764, SEQ ID NO. 2765, SEQ ID NO. 2766, SEQ ID NO. 2767, SEQ ID NO. 2768, SEQ ID NO. 2769, SEQ ID NO. 2770, SEQ ID NO. 2771, SEQ ID NO. 2772, SEQ ID NO. 2773, SEQ ID NO. 2774, SEQ ID NO. 2775, SEQ ID NO. 2776,SEQ ID NO:2777, SEQ ID NO:2778, SEQ ID NO:2779, SEQ ID NO:2780, SEQ ID NO:2781, SEQ ID NO:2782, SEQ ID NO:2783, SEQ ID NO:2784, SEQ ID NO:2785, SEQ ID NO:2786, SEQ ID NO:2787, SEQ ID NO:2788, SEQ ID NO:2789, SEQ ID NO:2790, SEQ ID NO:2791, SEQ ID NO:2792, SEQ ID NO:2793, SEQ ID NO:2794, SEQ ID NO:2795, SEQ ID NO:2796, SEQ ID NO:2797, SEQ ID NO:2798, SEQ ID NO:2799, SEQ ID NO:2800, SEQ ID NO:2801, SEQ ID NO:2802, SEQ ID NO:2803, SEQ ID NO:28 04, SEQ ID NO:2805, SEQ ID NO:2806, SEQ ID NO:2807, SEQ ID NO:2808, SEQ ID NO:2809, SEQ ID NO:2810, SEQ ID NO:2811, SEQ ID NO:2812, SEQ ID NO:2813, SEQ ID NO:2814, SEQ ID NO:2815, SEQ ID NO:2816, SEQ ID NO:2817, SEQ ID NO:2818, SEQ ID NO:2819, SEQ ID NO:2820, SEQ ID NO:2821, SEQ ID NO:2822, SEQ ID NO:2823, SEQ ID NO:2824, SEQ ID NO:2825, SEQ ID NO:2826, SEQ ID NO:2827, SEQ ID NO:2828, SEQ ID NO:2829, SEQ ID NO:2830, SEQ ID NO:2831, SEQ ID NO: 2832, SEQ ID NO:2833, SEQ ID NO:2834, SEQ ID NO:2835, SEQ ID NO:2836, SEQ ID NO:2837, SEQ ID NO:2838, SEQ ID NO:2839, SEQ ID NO:2840, SEQ ID NO:2841, SEQ ID NO:2842, SEQ ID NO:2843, SEQ ID NO:2844, SEQ ID NO:2845, SEQ ID NO:2846, SEQ ID NO:2847, SEQ ID NO:2848, SEQ ID NO:2849, SEQ ID NO:2850, SEQ ID NO:2851, SEQ ID NO:2852, SEQ ID NO:2853, SEQ ID NO:2854, SEQ ID NO:2855, SEQ ID NO:2856, SEQ ID NO:2857, SEQ ID NO:2858, SEQ ID NO:2859, SEQ ID NO: No. 2860, SEQ ID NO. 2861, SEQ ID NO. 2862, SEQ ID NO. 2863, SEQ ID NO. 2864, SEQ ID NO. 2865, SEQ ID NO. 2866, SEQ ID NO. 2867, SEQ ID NO. 2868, SEQ ID NO. 2869, SEQ ID NO. 2870, SEQ ID NO. 2871, SEQ ID NO. 2872, SEQ ID NO. 2873, SEQ ID NO. 2874, SEQ ID NO. 2875, SEQ ID NO. 2876, SEQ ID NO. 2877, SEQ ID NO. 2878, SEQ ID NO. 2879, SEQ ID NO. 2880, SEQ ID NO. 2881, SEQ ID NO. 2882, SEQ ID NO. 2883, SEQ ID NO. 2884, SEQ ID NO. 2885, SEQ ID NO. 2886, SEQ ID NO. 2887,SEQ ID NO:2888, SEQ ID NO:2889, SEQ ID NO:2890, SEQ ID NO:2891, SEQ ID NO:2892, SEQ ID NO:2893, SEQ ID NO:2894, SEQ ID NO:2895, SEQ ID NO:2896, SEQ ID NO:2897, SEQ ID NO:2898, SEQ ID NO:2899, SEQ ID NO:2900, SEQ ID NO:2901, SEQ ID NO:2902, SEQ ID NO:2903, SEQ ID NO:2904, SEQ ID NO:2905, SEQ ID NO:2906, SEQ ID NO:2907, SEQ ID NO:2908, SEQ ID NO:2909, SEQ ID NO:2910, SEQ ID NO:2911, SEQ ID NO:2912, SEQ ID NO:2913, SEQ ID NO:2914, SEQ ID NO:29 15, SEQ ID NO:2916, SEQ ID NO:2917, SEQ ID NO:2918, SEQ ID NO:2919, SEQ ID NO:2920, SEQ ID NO:2921, SEQ ID NO:2922, SEQ ID NO:2923, SEQ ID NO:2924, SEQ ID NO:2925, SEQ ID NO:2926, SEQ ID NO:2927, SEQ ID NO:2928, SEQ ID NO:2929, SEQ ID NO:2930, SEQ ID NO:2931, SEQ ID NO:2932, SEQ ID NO:2933, SEQ ID NO:2934, SEQ ID NO:2935, SEQ ID NO:2936, SEQ ID NO:2937, SEQ ID NO:2938, SEQ ID NO:2939, SEQ ID NO:2940, SEQ ID NO:2941, SEQ ID NO:2942, 2943, SEQ ID NO:2944, SEQ ID NO:2945, SEQ ID NO:2946, SEQ ID NO:2947, SEQ ID NO:2948, SEQ ID NO:2949, SEQ ID NO:2950, ​​SEQ ID NO:2951, SEQ ID NO:2952, SEQ ID NO:2953, SEQ ID NO:2954, SEQ ID NO:2955, SEQ ID NO:2956, SEQ ID NO:2957, SEQ ID NO:2958, SEQ ID NO:2959, SEQ ID NO:2960, SEQ ID NO:2961, SEQ ID NO:2962, SEQ ID NO:2963, SEQ ID NO:2964, SEQ ID NO:2965, SEQ ID NO:2966, SEQ ID NO:2967, SEQ ID NO:2968, SEQ ID NO:2969, SEQ ID NO:2970, SEQ ID NO: No. 2971, No. 2972, No. 2973, No. 2974, No. 2975, No. 2976, No. 2977, No. 2978, No. 2979, No. 2980, No. 2981, No. 2982, No. 2983, No. 2984, No. 2985, No. 2986, No. 2987, No. 2988, No. 2989, No. 2990, No. 2991, No. 2992, No. 2993, No. 2994, No. 2995, No. 2996, No. 2997, No. 2998,SEQ ID NO:2999, SEQ ID NO:3000, SEQ ID NO:3001, SEQ ID NO:3002, SEQ ID NO:3003, SEQ ID NO:3004, SEQ ID NO:3005, SEQ ID NO:3006, SEQ ID NO:3007, SEQ ID NO:3008, SEQ ID NO:3009, SEQ ID NO:3010, SEQ ID NO:3011, SEQ ID NO:3012, SEQ ID NO:3013, SEQ ID NO:3014, SEQ ID NO:3015, SEQ ID NO:3016, SEQ ID NO:3017, SEQ ID NO:3018, SEQ ID NO:3019, SEQ ID NO:3020, SEQ ID NO:3021, SEQ ID NO:3022, SEQ ID NO:3023, SEQ ID NO:3024, SEQ ID NO:3025, SEQ ID NO:30 26, SEQ ID NO:3027, SEQ ID NO:3028, SEQ ID NO:3029, SEQ ID NO:3030, SEQ ID NO:3031, SEQ ID NO:3032, SEQ ID NO:3033, SEQ ID NO:3034, SEQ ID NO:3035, SEQ ID NO:3036, SEQ ID NO:3037, SEQ ID NO:3038, SEQ ID NO:3039, SEQ ID NO:3040, SEQ ID NO:3041, SEQ ID NO:3042, SEQ ID NO:3043, SEQ ID NO:3044, SEQ ID NO:3045, SEQ ID NO:3046, SEQ ID NO:3047, SEQ ID NO:3048, SEQ ID NO:3049, SEQ ID NO:3050, SEQ ID NO:3051, SEQ ID NO:3052, SEQ ID NO:3053, 3054, SEQ ID NO:3055, SEQ ID NO:3056, SEQ ID NO:3057, SEQ ID NO:3058, SEQ ID NO:3059, SEQ ID NO:3060, SEQ ID NO:3061, SEQ ID NO:3062, SEQ ID NO:3063, SEQ ID NO:3064, SEQ ID NO:3065, SEQ ID NO:3066, SEQ ID NO:3067, SEQ ID NO:3068, SEQ ID NO:3069, SEQ ID NO:3070, SEQ ID NO:3071, SEQ ID NO:3072, SEQ ID NO:3073, SEQ ID NO:3074, SEQ ID NO:3075, SEQ ID NO:3076, SEQ ID NO:3077, SEQ ID NO:3078, SEQ ID NO:3079, SEQ ID NO:3080, SEQ ID NO:3081, No. 3082, SEQ ID NO. 3083, SEQ ID NO. 3084, SEQ ID NO. 3085, SEQ ID NO. 3086, SEQ ID NO. 3087, SEQ ID NO. 3088, SEQ ID NO. 3089, SEQ ID NO. 3090, SEQ ID NO. 3091, SEQ ID NO. 3092, SEQ ID NO. 3093, SEQ ID NO. 3094, SEQ ID NO. 3095, SEQ ID NO. 3096, SEQ ID NO. 3097, SEQ ID NO. 3098, SEQ ID NO. 3099, SEQ ID NO. 3100, SEQ ID NO. 3101, SEQ ID NO. 3102, SEQ ID NO. 3103, SEQ ID NO. 3104, SEQ ID NO. 3105, SEQ ID NO. 3106, SEQ ID NO. 3107, SEQ ID NO. 3108, SEQ ID NO. 3109,SEQ ID NO:3110, SEQ ID NO:3111, SEQ ID NO:3112, SEQ ID NO:3113, SEQ ID NO:3114, SEQ ID NO:3115, SEQ ID NO:3116, SEQ ID NO:3117, SEQ ID NO:3118, SEQ ID NO:3119, SEQ ID NO:3120, SEQ ID NO:3121, SEQ ID NO:3122, SEQ ID NO:3123, SEQ ID NO: 3124, SEQ ID NO:3125, SEQ ID NO:3126, SEQ ID NO:3127, SEQ ID NO:3128, SEQ ID NO:3129, SEQ ID NO:3130, SEQ ID NO:3131, SEQ ID NO:3132, SEQ ID NO:3133, SEQ ID NO:3134, SEQ ID NO:3135, SEQ ID NO:3136, SEQ ID NO:3137, SEQ ID NO:3138, SEQ ID NO:3139, SEQ ID NO:3140, SEQ ID NO:3141, SEQ ID NO:3142, SEQ ID NO:3143, SEQ ID NO:3144, SEQ ID NO:3145, SEQ ID NO:3146, SEQ ID NO:3147, SEQ ID NO:3148, SEQ ID NO:3149, SEQ ID NO:3150, SEQ ID NO:3151, SEQ ID NO:3152, SEQ ID NO:3153, SEQ ID NO:3154, SEQ ID NO:3155, SEQ ID NO:3156, SEQ ID NO:3157, SEQ ID NO:3158, SEQ ID NO:3159, SEQ ID NO:3160, SEQ ID NO:3161, SEQ ID NO:3162, SEQ ID NO:3163, SEQ ID NO:3164, SEQ ID NO:3165, SEQ ID NO:3166, SEQ ID NO:3167, SEQ ID NO:3168, SEQ ID NO:3169, SEQ ID NO:3170, SEQ ID NO:3171, SEQ ID NO:3172, SEQ ID NO:3173, SEQ ID NO:3174, SEQ ID NO:3175, SEQ ID NO:3176, SEQ ID NO:3177, SEQ ID NO:3178, SEQ ID NO:31 79, SEQ ID NO:3180, SEQ ID NO:3181, SEQ ID NO:3182, SEQ ID NO:3183, SEQ ID NO:3184, SEQ ID NO:3185, SEQ ID NO:3186, SEQ ID NO:3187, SEQ ID NO:3188, SEQ ID NO:3189, SEQ ID NO:3190, SEQ ID NO:3191, SEQ ID NO:3192, SEQ ID NO:3193, SEQ ID NO:3194, SEQ ID NO:3195, SEQ ID NO:3196, SEQ ID NO:3197, SEQ ID NO:3198, SEQ ID NO:3199, SEQ ID NO:3200, SEQ ID NO:3201, SEQ ID NO:3202, SEQ ID NO:3203, SEQ ID NO:3204, SEQ ID NO:3205, SEQ ID NO:3206, SEQ ID NO: No. 3207, No. 3208, No. 3209, No. 3210, No. 3211, No. 3212, No. 3213, No. 3214, No. 3215, No. 3216, No. 3217, No. 3218, No. 3219, No. 3220, No. 3221, No. 3222, No. 3223, No. 3224, No. 3225, No. 3226, No. 3227, No. 3228, No. 3229, No. 3230, No. 3231, No. 3232, No. 3233, No. 3234,SEQ ID NO:3235, SEQ ID NO:3236, SEQ ID NO:3237, SEQ ID NO:3238, SEQ ID NO:3239, SEQ ID NO:3240, SEQ ID NO:3241, SEQ ID NO:3242, SEQ ID NO:3243, SEQ ID NO:3244, SEQ ID NO:3245, SEQ ID NO:3246, SEQ ID NO:3247, SEQ ID NO:3248, SEQ ID NO:3249, SEQ ID NO:3250, SEQ ID NO:3251, SEQ ID NO:3252, SEQ ID NO:3253, SEQ ID NO:3254, SEQ ID NO:3255, SEQ ID NO:3256, SEQ ID NO:3257, SEQ ID NO:3258, SEQ ID NO:3259, SEQ ID NO:3260, SEQ ID NO:3261, SEQ ID NO:32 62, SEQ ID NO:3263, SEQ ID NO:3264, SEQ ID NO:3265, SEQ ID NO:3266, SEQ ID NO:3267, SEQ ID NO:3268, SEQ ID NO:3269, SEQ ID NO:3270, SEQ ID NO:3271, SEQ ID NO:3272, SEQ ID NO:3273, SEQ ID NO:3274, SEQ ID NO:3275, SEQ ID NO:3276, SEQ ID NO:3277, SEQ ID NO:3278, SEQ ID NO:3279, SEQ ID NO:3280, SEQ ID NO:3281, SEQ ID NO:3282, SEQ ID NO:3283, SEQ ID NO:3284, SEQ ID NO:3285, SEQ ID NO:3286, SEQ ID NO:3287, SEQ ID NO:3288, SEQ ID NO:3289, 3290, SEQ ID NO:3291, SEQ ID NO:3292, SEQ ID NO:3293, SEQ ID NO:3294, SEQ ID NO:3295, SEQ ID NO:3296, SEQ ID NO:3297, SEQ ID NO:3298, SEQ ID NO:3299, SEQ ID NO:3300, SEQ ID NO:3301, SEQ ID NO:3302, SEQ ID NO:3303, SEQ ID NO:3304, SEQ ID NO:3305, SEQ ID NO:3306, SEQ ID NO:3307, SEQ ID NO:3308, SEQ ID NO:3309, SEQ ID NO:3310, SEQ ID NO:3311, SEQ ID NO:3312, SEQ ID NO:3313, SEQ ID NO:3314, SEQ ID NO:3315, SEQ ID NO:3316, SEQ ID NO:3317, SEQ ID NO:3319, No. 3318, No. 3319, No. 3320, No. 3321, No. 3322, No. 3323, No. 3324, No. 3325, No. 3326, No. 3327, No. 3328, No. 3329, No. 3330, No. 3331, No. 3332, No. 3333, No. 3334, No. 3335, No. 3336, No. 3337, No. 3338, No. 3339, No. 3340, No. 3341, No. 3342, No. 3343, No. 3344, No. 3345,It may include SEQ ID NO:3346, SEQ ID NO:3347, SEQ ID NO:3348, SEQ ID NO:3349, SEQ ID NO:3350, SEQ ID NO:3351, SEQ ID NO:3352, SEQ ID NO:3353, SEQ ID NO:3354, SEQ ID NO:3355, SEQ ID NO:3356, SEQ ID NO:3357, SEQ ID NO:3358, SEQ ID NO:3359, SEQ ID NO:3360, or SEQ ID NO:3361. In yet further embodiments of this aspect, the CGI factor can comprise SEQ ID NO:5707, SEQ ID NO:5708, SEQ ID NO:5709, SEQ ID NO:5710, SEQ ID NO:5711, SEQ ID NO:5712, SEQ ID NO:5713, SEQ ID NO:5714, SEQ ID NO:5715, SEQ ID NO:5716, SEQ ID NO:5717, SEQ ID NO:5718, SEQ ID NO:5719, SEQ ID NO:5720, SEQ ID NO:5721, SEQ ID NO:5722, SEQ ID NO:5723, SEQ ID NO:5724, SEQ ID NO:5725, SEQ ID NO:5726, SEQ ID NO:5727, SEQ ID NO:5728, SEQ ID NO:5729, SEQ ID NO:5730, or SEQ ID NO:5731. In further embodiments of this aspect, which may be combined with any preceding embodiments, the CGI factor, CGI factor precursor, or CGI factor fragment is active and / or toxic. In additional embodiments of this aspect that may be combined with any preceding embodiment, the recombinant DNA construct comprises (a) at least one copy of a CGI element, (b) at least one copy of each of two or more CGI elements, (c) at least one CGI element precursor, (d) at least one CGI element fragment, (e) at least one CGI element motif, or (f) any combination of (a)-(e). In still further embodiments of this aspect that may be combined with any preceding embodiment, the heterologous promoter is a bacterial promoter, a fungal promoter, an algal promoter, an animal promoter, or a plant promoter. In yet further embodiments of this aspect that may be combined with any preceding embodiment, the heterologous promoter is a plant-expressible promoter, i.e., a promoter that functions to promote expression in a plant cell. In some embodiments of this aspect, the plant-expressible promoter is a ubiquitin promoter, a Cestrum yellows virus promoter, a corn TrpA promoter, an OsMADS 6 promoter, a corn H3 histone promoter,The heterologous promoter is selected from the group of promoters: corn sucrose synthetase 1 promoter, corn alcohol dehydrogenase 1 promoter, corn heat shock protein promoter, maize mtl promoter, endo small subunit RuBP carboxylase promoter, rice actin promoter, rice cyclophilin promoter, Ti plasmid mannopine synthase promoter, Ti plasmid nopaline synthase promoter, petunia chalcone isomerase promoter, bean glycine rich protein 1 promoter, potato patatin promoter, lectin promoter, CaMV 35S promoter, or S-E9 small subunit RuBP carboxylase promoter. In some embodiments, the heterologous promoter is an inducible promoter, a tissue-specific promoter, a time-specific promoter, or a developmental stage-specific promoter. Tissue-specific promoters are useful for restricting the expression of the recombinant DNA construct and the encoded CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif to a specific tissue (e.g., root, leaf, tuber, fruit, or seed) of a plant. In some embodiments, the heterologous promoter is a plant miRNA promoter, which can be inducible, tissue-specific, time-specific, or developmental stage-specific, see, for example, the tissue-specific promoters disclosed in U.S. Pat. No. 8,334,430 and the time-specific promoters disclosed in U.S. Pat. No. 8,314,290. In some embodiments, the recombinant DNA construct comprises additional elements useful for expression control, such as expression-enhancing elements, transcription-stabilizing sequences, riboswitches, or recognition sites for miRNAs or siRNAs. For example, the inclusion of a recognition site for a miRNA that is naturally expressed in a particular tissue of a plant is expected to reduce or eliminate expression of a CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif in the particular tissue. In an additional embodiment of this aspect, the recombinant DNA construct further comprises a nucleotide sequence encoding at least one secretory signal peptide functional in the cell. Yet another aspect of the present disclosure isThe present invention relates to a recombinant vector comprising the recombinant DNA construct of any one of the preceding embodiments. In some embodiments of this aspect, the vector comprises a left T-DNA border sequence and a right T-DNA border sequence flanking the recombinant DNA construct. In some embodiments, the vector further comprises additional sequences flanking the recombinant DNA construct. The additional sequences may represent selectable markers, transposon ends, homology arms, restriction sites, or other sequences suitable for downstream use of the vector. In additional embodiments of this aspect, the vector is a bacterial, viral, or viroid vector.

[0020] A further aspect of the present disclosure pertains to an RNA transcript (e.g., messenger RNA) resulting from transcription of the recombinant DNA construct of any one of the preceding embodiments.

[0021] An additional aspect of the present disclosure relates to a CGI factor, a CGI factor precursor, a CGI factor fragment, or a CGI factor motif encoded by the recombinant DNA construct of any one of the preceding embodiments.

[0022] Transgenic Cells and Organisms Yet another aspect of the disclosure relates to a transgenic cell comprising a recombinant vector of any one of the preceding claims. In further embodiments of this aspect, the cell is selected from a bacterial cell, a fungal cell, an algae cell, an animal cell, or a plant cell. In additional embodiments of this aspect, the transgenic cell is a plant cell. In some embodiments of this aspect, the plant cell is a dicotyledonous plant cell. In further embodiments of this aspect, the dicotyledonous plant cell is selected from the group of a soybean cell, a sunflower cell, a tomato cell, a potato cell, a Brassica spp. cell, a cotton cell, a sugar beet cell, or a tobacco cell. In additional embodiments of this aspect, the plant cell is a monocotyledonous plant cell. In further embodiments of this aspect, the monocotyledonous plant cell is selected from the group of a barley cell, a corn cell, an oat cell, a rice cell, a sorghum cell, a sugarcane cell, or a wheat cell. In yet another embodiment of this aspect, which may be combined with any of the preceding embodiments having a transgenic cell, the CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is (a) transiently expressed, or (b) stably expressed.

[0023] Additional aspects of the disclosure relate to transgenic plants comprising the transgenic plant cells of any of the preceding embodiments. In some embodiments, the transgenic plant is a chimera having some cells that are transgenic (e.g., express a recombinant DNA construct as disclosed herein) and some cells that are not transgenic. Related embodiments include grafted plants, where the rootstock is transgenic (e.g., expresses a recombinant DNA construct as disclosed herein) and the grafted scion is not transgenic, or the rootstock is not transgenic and the scion is transgenic. In embodiments, the modified genome is the nuclear genome of the plant, and in other embodiments, the modified genome is the chloroplast or mitochondrial genome of the plant. In some embodiments of this aspect, the transgenic plant is a dicotyledonous plant. In further embodiments of this aspect, the dicotyledonous plant is selected from the group of a soybean plant, a sunflower plant, a tomato plant, a brassica plant, a cotton plant, a sugar beet plant, or a tobacco plant. In additional embodiments of this aspect, the transgenic plant is a monocotyledonous plant. In a further embodiment of this aspect, the monocotyledonous plant is selected from the group of an barley plant, a corn plant, an oat plant, a rice plant, a sorghum plant, a sugarcane plant, or a wheat plant, hi yet another embodiment of this aspect, the plant has improved resistance to fungal pathogens compared to a control plant not comprising the transgenic plant cell.In yet another embodiment of this aspect, the fungal pathogen is one of Aspergillus spp.; Magnaporthe oryzae; Botrytis cinerea; Puccinia spp.; Fusarium graminearum; Fusarium oxysporum; Blumeria graminis; Mycosphaerella graminicola; Colletotrichum spp.; Ustilago maydis; Melampsora lini; Phakopsora pachyrhizi; or Rhizoctonia solani. In another embodiment of this aspect that may be combined with any of the preceding embodiments, the nucleotide sequence encoding the CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is not present in the genome of the fungal pathogen.

[0024] The plants and plant cells may be of any species of interest, including dicotyledons and monocotyledons. Plants of interest include row crops, fruit producing plants and trees, vegetables, trees, and ornamental plants, including ornamental flowers, shrubs, trees, ground covers, and turf. Examples of commercially important cultivated crops, trees, and plants include alfalfa (Medicago sativa), almonds (Prunus dulcis), apples (Malus x domestica), apricots (Prunus armeniaca, P. brigantine, P. mandshurica, P. mume, P. sibirica), artichokes (Cynara cardunculus var. scolymus), asparagus (Asparagus officinalis), avocados (Persea americana), bananas (Musa spp.), barley (Hordeum vulgare), beans (Phaseolus spp.), blueberries and cranberries (Vaccinium spp.), Brazil nuts (Bertholletia excelsa), cacao (Theobroma cacao), calamansi (Citrus x microcarpa), canola and rapeseed or oilseed rape (Brassica napus), Polish canola (Brassica rapa) and related cruciferous vegetables including broccoli, kale, cabbage, and turnip (Brassica carinata, B. juncea, B. oleracea, B. napus, B. nigra, and B. rapa, and hybrids thereof), carnation (Dianthus caryophyllus), carrot (Daucus carota sativus), cashew (Anacardium occidentale), cassava (Manihot esculentum), celery (Apium graveolens), cherry (Prunus avium), chestnut (Castanea spp.), chickpea or garbanzo (Cicer arietinum), chicory (Cichorium intybus), chili pepper and hot pepper (Capsicum anguicida). annuum, C.C. frutescens, C. chinense, C. pubescens, C. baccatum, chrysanthemum (Chrysanthemum spp.), citron (Citrus medica), coconut (Cocos nucifera), coffee (wild and cultivated Coffea spp. including Coffea arabica, Coffea canephora, and Coffea liberica), cotton (Gossypium hirsutum L.), cowpea (Vigna unguiculata and other Vigna spp.), broad bean (Vicia faba), cucumber (Cucumis sativus), currants and gooseberries (Ribes spp.), dates (Phoenix dactylifera), duckweed (family Lemnaceae), Lemnoideae), eggplant or aubergine (Solanum melongena), elderberry (Sambucus spp.), eucalyptus (Eucalyptus spp.), flax (Linum usitatissumum L.), geranium (Pelargonium spp.), ginger (Zingiber officinale), ginseng (Panax spp.), grapefruit (Citrus x paradisi), grapes (Vitis spp.), including wine grapes (Vitis vinifera and their hybrids), guava (Psidium guajava), hazelnuts (Corylus avellana, Corylus spp.), hemp and cannabis (Cannabis sativa and Cannabis spp.), hops (Humulus lupulus), horseradish (Armoracia rusticana), iris (Iris spp.), jackfruit (Artocarpus heterophyllus), kiwifruit (Actinidia spp.), kumquat (Citrus japonica), lemon (Citrus limon), lentil (Lens culinaris), lettuce (Lactuca sativa), lime (Citrus spp.), litchi (Litchi chinensis), macadamia (Macadamia spp.), corn (Zea mays L.), mandarin (Citrus reticulata), mango (Mangifera indica), mangosteen (Garcinia mangostana), melon (Cucumis melo), millet (Setaria spp., Echinochloa spp., Eleusine spp., Panicum spp.), spp., Pennisetum spp.), oats (Avena sativa), oil palm (Ellis quineensis), okra (Abelmoschus esculentus), olives (Olea europaea), onions (Allium cepa) and other alliums (Allium spp.), oranges (Citrus sinensis), papaya (Carica papaya), parsnips (Pastinaca sativa), passion fruit (Passiflora edulis), pecans (Carya illinoinensis), peaches and nectarines (Prunus persica), pears (Pyrus spp.), peas (Pisum sativum), peanuts (Arachis hypogaea), peonies (Paeonia spp.), persimmons (Diospyros kaki (Diospyros spp.), petunia (Petunia spp.), pineapple (Ananas comosus), pistachio (Pistacia vera), plantain (Musa spp.), plums (Prunus domestica), poinsettias (Euphorbia pulcherrima), pomelo (Citrus maxima), poplars (Populus spp.), potatoes (Solanum tuberosum), pumpkins and squash (Cucurbita pepo, C. maxima, C. moschata), quince (Cydonia oblonga), raspberries (Rubus idaeus, Rubus occidentalis, Rubus spp.), rhubarb (Rheum spp.), rice (Oryza sativa L.), roses (Rosa spp.), rubber (Hevea brasiliensis), rye (Secale cereale), safflower (Carthamus tinctorius) L), Satsuma mandarin (Citrus unshiu), sesame seed (Sesame indium), sorghum (Sorghum bicolor), bitter orange (Citrus x aurantium), soursop (Annona muricata), soybean (Glycine max L.), strawberry (Fragaria spp., Fragaria x ananassa), sugar beet (Beta vulgaris), sugar cane (Saccharum spp.), sunflower (Helianthus annuus), sweet potato (Ipomoea batatas), tamarind (Tamarindus indica), tangerine (Citrus tangerina), tea (Camellia sinensis), tobacco (Nicotiana tabacum L.), tomatillo (Physalis philadelphica), tomato (Solanum lycopersicum or Lycopersicon esculentum, tulips (Tulipa spp.), walnuts (Juglans spp. L.), watermelon (Citrulus lanatus), wheat (Triticum aestivum), and yams (Discorea spp.)). Wild relatives of cultivated plants are also of interest.

[0025] A further aspect of the present disclosure relates to a transgenic seed of the transgenic plant of any of the preceding embodiments, the seed comprising a recombinant DNA construct.

[0026] An additional aspect of the present disclosure relates to an F1 progeny plant having as at least one parent the transgenic plant of any of the preceding embodiments, wherein the F1 progeny plant comprises any of the recombinant DNA constructs of the preceding embodiments.

[0027]

[0013] Yet another aspect of the present disclosure relates to a harvest product produced from the transgenic plant of any of the preceding embodiments, wherein the harvest product comprises a recombinant DNA construct. In some embodiments of this aspect, the harvest product is a fruit, a leaf, a stem, a flower, a root, a tuber, or a seed.

[0028] An additional aspect of the present disclosure relates to a plant having a genome that has been modified to express a heterologous DNA sequence encoding a polypeptide comprising at least one conidial germination inhibitor (CGI) factor, CGI factor precursor, CGI factor fragment, or CGI factor motif, optionally fused to at least one plant secretory signal peptide, wherein the CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif inhibits conidial germination, growth, or reproduction of a fungal pathogen of the plant, and the CGI factor is selected from the group consisting of SEQ ID NO: The plant has an amino acid sequence having at least 80% sequence identity with a sequence selected from the group consisting of SEQ ID NOs: 961-1920, 1957-2189, 2194-2210, 2215-2243, 2457-3361, or 5707-5731, or the CGI factor motif comprises at least one of SEQ ID NOs: 1921-1956, and the plant has improved resistance to fungal pathogens compared to a control plant not expressing the heterologous DNA sequence. The nucleotides encoding the at least one CGI factor may comprise SEQ ID NOs: 1-960 or 3362-5698. In additional embodiments of this aspect, the nucleotide sequence of the at least one CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is not present in the genome of the fungal pathogen.In further embodiments of this aspect that may be combined with any preceding embodiments, the fungal pathogen is one of Aspergillus spp.; Magnaporthe oryzae; Botrytis cinerea; Puccinia spp.; Fusarium graminearum; Fusarium oxysporum; Blumeria graminis; Mycosphaerella graminicola; Colletotrichum spp.; Ustilago maydis; Melampsora lini; Phakopsora pachyrhizi; or Rhizoctonia solani.

[0029] Yet another aspect of the present disclosure relates to a plant comprising a cell containing a recombinant DNA construct comprising a heterologous promoter for expressing a CGI factor, a CGI factor precursor, a CGI factor fragment, or a CGI factor motif and functional in the cell, the heterologous promoter being operably linked to a nucleic acid molecule comprising (a) a nucleotide sequence encoding at least one conidial germination inhibitor (CGI) factor, a CGI factor precursor, a CGI factor fragment, or a CGI factor motif, and (b) a nucleotide sequence encoding at least one secretory signal peptide functional in the cell, wherein the CGI factor is selected from the group consisting of SEQ ID NOs: 961-192. 0, SEQ ID NO: 1957-2189, SEQ ID NO: 2194-2210, SEQ ID NO: 2215-2243, SEQ ID NO: 2457-3361, or SEQ ID NO: 5707-5731, or the CGI factor motif comprises at least one of SEQ ID NO: 1921-1956, and the nucleotide sequence encoding the at least one CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif optionally comprises at least one codon optimized for expression in the cell. The nucleotide sequence encoding the at least one CGI factor may comprise SEQ ID NO: 1-960 or 3362-5698. In some embodiments of this aspect, the CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is active and / or toxic. In further embodiments of this aspect that may be combined with any preceding embodiment, the cell is a plant cell. In additional embodiments of this aspect that may be combined with any preceding embodiment having a cell that is not a plant cell, the cell is a bacterial or fungal cell in or on the plant. In some embodiments of this aspect that may be combined with any preceding embodiment, the plant has improved resistance to fungal pathogens compared to a control plant that does not include the cell.In yet another embodiment of this aspect, the fungal pathogen is one of Aspergillus spp., Magnaporthe oryzae, Botrytis cinerea, Puccinia spp., Fusarium graminearum, Fusarium oxysporum, Blumeria graminis, Mycosphaerella graminicola, Colletotrichum spp., Ustilago maydis, Melampsora linifera, Kopsora pachyrhizi, or Rhizoctonia solani. In yet another embodiment of this aspect that may be combined with any preceding embodiment, the nucleotide sequence encoding at least one CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is not present in the genome of the fungal pathogen.

[0030] composition Yet another aspect of the present disclosure relates to an antifungal or fungicidal composition comprising the CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif of any one of the preceding embodiments and an agriculturally acceptable carrier. In some embodiments of this aspect, the composition is formulated as one of a seed treatment, a foliar spray treatment, a foliar dip treatment, a ready-to-use (RTU) formulation, a produce coating, a suspension concentrate, a tank mix, an aerosol, a root dip, a dip, a spray, a soil treatment, an irrigation formulation, or a sprinkler formulation. In further embodiments of this aspect, the agriculturally acceptable carrier includes a solid carrier, a liquid carrier, a gel carrier, a suspension, or an emulsion. In additional embodiments of this aspect, the agriculturally acceptable carrier includes one or more of an adjuvant, an inert ingredient, a dispersant, a surfactant, a tackifier, a binder, or a stabilizer. Adjuvants and other ingredients useful in agricultural formulations are described, for example, in Compedium of Herbicidal Adjuvants, 13 available at siu-weeds[dot]com / adjuvants / index-adj[dot]html. thedition, 2016. In some embodiments of this aspect, such agricultural formulations further comprise one or more additional components, such as herbicides, insecticides, nematicides, fungicides (other than the CGI factors, CGI factor precursors, CGI factor fragments, or CGI factor motifs disclosed herein), attractants, or baits. In some embodiments of this aspect, the composition is formulated for application to human-constructed structures (e.g., buildings, fences, walls) or man-made objects (e.g., furniture, clothing, fabrics), or for incorporation into materials useful for making human-constructed structures or man-made objects. In some embodiments of this aspect, the composition is incorporated as an additive to food or feed, e.g., products processed from plants. In additional embodiments of this aspect, the composition is formulated as a sustained- or controlled-release formulation.

[0031] An additional aspect of the present disclosure relates to an antifungal composition comprising an effective amount of at least one conidial germination inhibition (CGI) factor, CGI factor precursor, CGI factor fragment, or CGI factor motif, the antifungal composition comprising: (a) a sequence selected from the group consisting of SEQ ID NOs: 961-1920, 1957-2189, 2194-2210, 2215-2243, 2457-3361, or 5707-5731, and at least 50%, at least 5 ... %, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the CGI factor, or (b) an amino acid sequence of a CGI factor motif, and a carrier. In some embodiments of this aspect, the CGI factor motif comprises at least one of SEQ ID NOs: 1921-1956. In additional embodiments of this aspect that may be combined with any preceding embodiment, the CGI factor, CGI factor precursor, or CGI factor fragment is active and / or toxic. In further embodiments of this aspect that may be combined with any preceding embodiment, the carrier is selected from an agriculturally acceptable carrier or a pharma- ceutically acceptable carrier. In additional embodiments of this aspect that can be combined with any preceding embodiment, the composition is formulated as a liquid, gel, emulsion, suspension, encapsulant, solid, powder, coating, spray, soil soak, granule, seed coat, or bait. In some embodiments of this aspect, such agricultural formulations further comprise one or more additional components, such as herbicides, insecticides, nematicides, fungicides (other than the CGI factors, CGI factor precursors, CGI factor fragments, or CGI factor motifs disclosed herein), attractants, or bait. In some embodiments of this aspect, the composition is formulated for application to human-constructed structures (e.g., buildings, fences, walls) or man-made objects (e.g., furniture, clothing, fabrics), or for incorporation into materials useful for making human-constructed structures or man-made objects.In some embodiments of this aspect, the composition is incorporated as an additive into a food or feed, e.g., a product processed from a plant. In additional embodiments of this aspect, the composition is formulated as a sustained or controlled release formulation.

[0032] Yet another aspect of the present disclosure relates to a composition having antimicrobial properties comprising a substrate or matrix complexed with at least one conidial germination inhibition (CGI) factor, CGI factor precursor, CGI factor fragment, or CGI factor motif that is active and / or toxic, wherein the CGI factor is a sequence selected from the group of SEQ ID NOs: 961-1920, SEQ ID NOs: 1957-2189, SEQ ID NOs: 2194-2210, SEQ ID NOs: 2215-2243, SEQ ID NOs: 2457-3361, or SEQ ID NOs: 5707-5731, and at least 5 or the CGI factor motif comprises at least one of SEQ ID NOs: 1921-1956. In some embodiments of this aspect, the CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is active and / or toxic. In further embodiments of this aspect, which may be combined with any preceding embodiment, complex formation between the substrate or matrix and the at least one CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is by (a) covalent bonding, (b) non-covalent bonding, or (c) a combination of (a) and (b). In some embodiments of this aspect, the substrate or matrix comprises a polypeptide. In additional embodiments of this aspect, which may be combined with any preceding embodiment having a substrate or matrix, the substrate or matrix comprises a self-assembling peptide.

[0033] Any suitable substrate or matrix known to one of skill in the art can be applied to the present disclosure. In some embodiments, the substrate or matrix comprises a polypeptide. In some embodiments, the polypeptide is a self-assembling peptide. In some embodiments, the self-assembling peptide is (M)(YEYK) n YEY (SEQ ID NO: 2194), where n=3 or n is 3-10, and methionine is any amino acid at the terminal and is covalently or non-covalently linked to one or more CGI peptides. Self-assembling peptides are known to those of skill in the art, as demonstrated by Miki et al. (2021) Nature Communications, 21:3412, DOI: 10.1038 / s41467-021-23794-6, which is specifically and entirely incorporated by reference for all that it teaches. In some embodiments, the complexation between the substrate or matrix and at least one CGI peptide is by covalent bonding. In some embodiments, the complexation between the substrate or matrix and at least one CGI peptide is by non-covalent bonding. In some embodiments, the complexation between the substrate or matrix and at least one CGI peptide is by a combination of covalent and non-covalent bonding.

[0034] Methods of Providing Fungal Resistance A further aspect of the present disclosure relates to a method for providing an organism with resistance to a fungal pathogen of the organism, comprising expressing in a cell of the organism a combination DNA construct of any one of the preceding embodiments, wherein a heterologous promoter functions in the organism. In a further embodiment of this aspect, the nucleotide sequence encoding the CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is not present in the genome of the fungal pathogen. In an additional embodiment of this aspect, the recombinant DNA construct is introduced into the cell of the organism by (a) transfection, (b) inheritance from a parent cell, or (c) fusion with a donor cell containing the recombinant DNA construct. In yet another embodiment of this aspect, the organism is a plant, and the recombinant DNA construct is provided to the plant by (a) transformation, or (b) inheritance from at least one parent plant that contained the recombinant DNA construct. The transformation may be stable or transient. In yet another embodiment of this aspect, the plant is selected from the group of a corn plant, a soybean plant, a wheat plant, a rice plant, a cotton plant, a potato plant, a tomato plant, a Brassica plant, or a sugar beet plant.

[0035] An additional aspect of the present disclosure relates to a method of providing an organism with resistance to a fungal pathogen of the organism, comprising contacting the organism with the vector of any of the preceding embodiments. In a further embodiment of this aspect, the nucleotide sequence encoding the CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is not present in the genome of the fungal pathogen.

[0036] Yet another aspect of the present disclosure relates to a method of providing an organism with resistance to a fungal pathogen of the organism, comprising contacting the organism with a cell of any of the preceding embodiments. In some embodiments of this aspect, the nucleotide sequence encoding the CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is not present in the genome of the fungal pathogen.

[0037] Yet another aspect of the present disclosure is a method of producing a disease resistant plant, comprising introducing into the plant a recombinant DNA construct of any one of the preceding embodiments, wherein a CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is expressed in the plant; and at least one of SEQ ID NOs: 961-1920, 1957-2189, 2194-2210, 2215-2243, 2457-3361, or 5707-5731, and at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 85%, at least 90%, at least 9 ... and editing the plant to express a CGI factor, a CGI factor precursor, or a CGI factor fragment, or editing the plant to express a CGI factor motif, comprising an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity, thereby producing a disease resistant transgenic plant. In some embodiments of this aspect, the CGI factor motif comprises at least one of SEQ ID NOs: 1921-1956. The nucleotides encoding the at least one CGI factor may comprise SEQ ID NOs: 1-960 or 3362-5698. In additional embodiments of this aspect that may be combined with any preceding embodiment, the CGI factor, CGI factor precursor, or CGI factor fragment is active and / or toxic.In further embodiments of this aspect that may be combined with any preceding embodiment, editing the plant is performed using zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), oligonucleotide-directed mutagenesis (ODM), or clustered regularly interspaced short palindromic repeats (CRISPR) nucleases (e.g., Cas9, Cas12), or by gene writing (see, e.g., PCT Patent Application Publication No. WO2020 / 047124). In yet another embodiment of this aspect that may be combined with any preceding embodiment, the introducing step is accomplished by (a) transforming the plant, or (b) crossing a first plant containing the recombinant DNA construct with a second plant. In yet another embodiment of this aspect that may be combined with any preceding embodiment, the introducing step comprises transforming the plant, and transforming the plant comprises bacterial-mediated transformation, microprojectile-mediated transformation, sonication, electroporation, nanoparticle-mediated transformation, or liposome- or spheroplast-mediated vector delivery. Additional embodiments of this aspect that may be combined with any preceding embodiment include the plant being a corn plant, a soybean plant, a wheat plant, a rice plant, a cotton plant, a potato plant, a tomato plant, a Brassica spp. plant, or a sugar beet plant.

[0038] Some aspects of the present disclosure relate to a method of providing an organism with resistance to a fungal pathogen of the organism, comprising contacting the organism with the antifungal composition of any one of the preceding embodiments. In further embodiments of this aspect, the amino acid sequence of the CGI factor is not the amino acid sequence of an alpha pheromone naturally expressed by the fungal pathogen, or the nucleotide sequence encoding the CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is not present in the genome of the fungal pathogen.

[0039] In some embodiments, the present disclosure provides resistance to a fungal pathogen selected from the group consisting of Aspergillus, Candida, Coccidioides, Histoplasma, or Blastomyces fungi. In some embodiments, the fungal pathogen is selected from the group consisting of Mucoromycotina fungi, Candida spp. (e.g., C. albicans, C. tropicalis, C. krusei, C. glabrata, and C. pseudotropicalis), Aspergillus spp. (e.g., A. fumigatus, A. flavus, and A. niger), Magnaporthe oryzae; Botrytis cinerea, Puccinia spp., Fusarium graminearum, Fusarium oxysporum, Blumeria graminis; Mycosphaerella graminis. graminicola, Colletotrichum spp., Ustilago maydis, Melampsora lini, Phakopsora pachyrhizi, or Rhizoctonia solani. In some embodiments, the methods of the present disclosure provide resistance to a plant fungal pathogen.In some embodiments, the plant fungal pathogen is Magnaporthe oryzae; Botrytis cinerea; Puccinia spp.; Fusarium graminearum; Fusarium oxysporum; Blumeria graminis; Mycosphaerella graminicola; Colletotrichum spp.; Ustilago maydis; Melampsora lini; Phakopsora pachyrhizi; or Rhizoctonia solani.

[0040] Methods for controlling or preventing fungal growth A further aspect of the present disclosure relates to a method of controlling a fungal pathogen, comprising delivering to the fungal pathogen or its environment an effective amount of a CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif of any one of the preceding embodiments.

[0041] A further aspect of the present disclosure relates to a method for controlling a fungal pathogen, the method comprising applying to a fungal pathogen or a locus containing the fungal pathogen a composition comprising a conidial germination inhibitor (CGI) factor, a CGI factor precursor, a CGI factor fragment, or a CGI motif derived from at least one of the fungal pathogen, a fungus of the same genus as the fungal pathogen, a fungus of a different genus from the fungal pathogen, or a mixture thereof. In some embodiments of this aspect, the CGI factor has an amino acid sequence selected from the group of SEQ ID NOs: 961-1920, 1957-2189, 2194-2210, 2215-2243, 2457-3361, or 5707-5731, or an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity thereto, or the CGI factor motif comprises at least one of SEQ ID NOs: 1921-1956. The nucleotides encoding at least one CGI factor may comprise SEQ ID NOs: 1-960 or 3362-5698. In additional embodiments of this aspect that may be combined with any preceding embodiment, the CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is active and / or toxic. As used herein, a CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif "derived" from a fungal pathogen refers to a CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif obtained directly (e.g., extracted) or indirectly from a fungal pathogen (e.g., a synthetic CGI factor or precursor thereof having a sequence based on one or more fungal pathogen CGI factor sequences).In some embodiments, the amino acids of a CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif "derived" from a fungal pathogen correspond to the amino acid sequence of a naturally occurring fungal alpha pheromone peptide, e.g., have an amino acid sequence that is identical or nearly identical (e.g., >90% sequence identity) to a genomically encoded, expressed, or putative alpha pheromone peptide sequence of the fungal pathogen. In embodiments, the amino acid sequence of a CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif "derived" from a fungal pathogen comprises a combination of two or more naturally occurring fungal alpha pheromone peptides, e.g., a homodimer of a single fungal alpha pheromone peptide or a heterodimer of two different alpha pheromone peptides, or a multimer of one or more alpha pheromone peptides with or without additional amino acids (e.g., adjacent to or linked to amino acids adjacent to or between the alpha pheromone monomers). In other embodiments, the sequence of a CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif "derived" from a fungal pathogen is shorter or longer than its sequence in the fungal pathogen. For example, a synthetic CGI factor or CGI factor precursor can include additional amino acids inserted into the sequence of a naturally occurring fungal alpha pheromone (or alpha pheromone precursor) sequence, and in embodiments, the additional amino acids provide a desired property or function compared to a polypeptide lacking the additional amino acids, such as, but not limited to, increased solubility, altered charge, improved detectability or selectability (e.g., using a detectable or selectable sequence such as a reporter or epitope), increased stability, increased cell permeability, or modified cell or tissue location (e.g., localization to an organelle or specific tissue). In some embodiments, the synthetic CGI factors or CGI factor precursors comprise sequences derived from a number of naturally occurring CGI factors identified from one or more fungal pathogens (e.g., synthetic CGI factors that are CGI factor sequences identified from fungal species with different unit sequences, optionally in the form of heterodimers or other multimers with linker amino acids joining the unit sequences).Furthermore, a CGI factor, CGI factor precursor, CGI factor fragment, or CGI motif "derived" from a fungal pathogen may have additional amino acid residues added to it, such as a linker sequence, a signal peptide sequence, or the like.

[0042] An additional aspect of the present disclosure relates to a method of controlling fungal growth or reproduction, comprising providing to a fungus an effective amount of at least one conidial germination inhibitor (CGI) factor, CGI factor precursor, CGI factor fragment, or CGI factor motif, wherein the CGI factor has at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 90%, at least 10 ... or the CGI factor motif comprises an amino acid sequence having at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the CGI factor motif; or the CGI factor motif comprises at least one of SEQ ID NOs: 1921-1956, and the amino acid sequence of the CGI factor is not an amino acid sequence of an alpha pheromone naturally expressed by the fungus; or the nucleotide sequence of the at least one CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is not present in the genome of the fungus. The nucleotides encoding the at least one CGI factor may comprise SEQ ID NOs: 1-960 or 3362-5698. In some embodiments of this aspect, the CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is active and / or toxic. In further embodiments of this aspect that may be combined with any preceding embodiments, the composition is provided to the fungus by directly contacting the fungus with the composition, or by delivering the composition to the environment of the fungus.

[0043] Yet another aspect of the present disclosure relates to a method of preventing fungal growth on a surface, comprising treating the surface with an effective amount of a composition comprising at least one conidial germination inhibitor (CGI) factor, CGI factor precursor, CGI factor fragment, or CGI factor motif, wherein the CGI factor is selected from the group consisting of SEQ ID NOs: 961-1920, SEQ ID NOs: 1957-2189, SEQ ID NOs: 2194-2210, SEQ ID NOs: 2215-2243, SEQ ID NOs: 2457-3361, or SEQ ID NOs: 5707-5731, and at least one CGI factor precursor, CGI factor fragment, or CGI factor motif. or the CGI factor motif comprises at least one of SEQ ID NOs: 1921-1956. The nucleotides encoding at least one CGI factor may comprise SEQ ID NOs: 1-960 or 3362-5698. In some embodiments of this aspect, the CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is active and / or toxic. In further embodiments of this aspect that may be combined with any preceding embodiment, the surface is a non-biological surface or is a surface of a living organism. In additional embodiments of this aspect that may be combined with any preceding embodiments, the nucleotide sequence of at least one CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is not present in the genome of a fungus.

[0044] Also provided herein are methods of preventing fungal growth on a surface or in a structure (e.g., a human-constructed structure or man-made object). In some embodiments, the methods include treating the surface or structure with a composition (e.g., a paint, coating, spray, dip) that includes an effective amount of at least one CGI factor, CGI factor precursor, CGI factor fragment, or CGI motif that inhibits fungal growth or reproduction. In some embodiments, the CGI factor comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 961 to 1920, or a sequence selected from the group consisting of SEQ ID NOs: 1957 to 2189, or a sequence selected from the group consisting of SEQ ID NOs: 2194 to 2210, or a sequence selected from the group consisting of SEQ ID NOs: 2215 to 2243, or a sequence selected from the group consisting of SEQ ID NOs: 2457 to 3361, or a sequence selected from the group consisting of SEQ ID NOs: 5707 to 5731. In embodiments, the nucleotide sequence encoding the at least one CGI factor comprises at least one sequence selected from the group consisting of SEQ ID NOs: 1-960, or 3362-5698. In some embodiments, the DNA sequence of the at least one CGI factor, CGI factor precursor, CGI factor fragment, or CGI motif is not present in the genome of the fungus.

[0045] In some embodiments, the surface is a non-biological surface. In some embodiments, the surface is a surface of a living organism. In embodiments, the structure is a human constructed structure or man-made object, such as a building, a fence, a wall, furniture, fabric, or components thereof.

[0046] Methods for Treating Fungal Diseases A further aspect of the present disclosure relates to a method of treating a subject with a fungal disease, comprising administering to the subject an antifungal or fungicidal composition comprising any of the CGI factors, CGI factor precursors, CGI factor fragments, or CGI factor motifs of the preceding embodiments and a pharmaceutically acceptable carrier. In some embodiments of this aspect, the subject is a mammal, and in other embodiments, the subject is a vertebrate, such as a bird, a reptile, a fish, or an amphibian, or an invertebrate, such as an insect. In additional embodiments of this aspect, the mammal is a human. In further embodiments of this aspect, the mammal is a domestic or livestock animal. In still further embodiments of this aspect, which can be combined with any of the preceding embodiments, the fungal disease is caused by a fungal pathogen selected from the group of Aspergillus, Candida, Coccidioides, Histoplasma, Cryptococcus, Pneumocystis, or Blastomyces fungi.In some embodiments, the fungal disease is caused by Mucoromycotina fungi, Candida spp. (e.g., C. albicans, C. auris, C. tropicalis, C. krusei, C. glabrata, C. parapsilosis, and C. pseudotropicalis), Cosidioides spp. (C. immitis or C. posadaci), Aspergillus spp. (e.g., A. fumigatus, A. flavus, and A. niger), Mucocomyces spp., Rhizomucor spp., Malassezia spp. (e.g., M. furfur, M. globosa, M. restricta), Magnaporthe oryzae, Botrytis cinerea, Puccinia spp.; Fusarium graminearum, Fusarium oxysporum, oxysporum, Blumeria graminis, Mycosphaerella graminicola, Colletotrichum spp., Ustilago maydis, Melampsora lini, Phakopsora pachyrhizi, or Rhizoctonia solani. In yet another embodiment of this aspect that may be combined with any preceding embodiment, the fungal disease is aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, mucormycosis, mycetoma, tinea, sporotrichosis, paracoccidioidomycosis, talaromycosis, chromoblastomycosis, fusariosis, emergomycosis, scedosporiosis, or fungal meningitis. In an additional embodiment of this aspect that may be combined with any preceding embodiment, the antifungal or fungicidal composition is administered intravenously, intramuscularly, subcutaneously, topically, orally, transdermally, intraperitoneally, intraorbitally, by implantation, by inhalation, intrathecally, intraventricularly, or intranasally.

[0047] As used herein, the term "subject" refers to an organism such as an animal, a plant, or a microorganism. In some embodiments, the subject is a mammal. In some embodiments, the mammal is a human. In other embodiments, the subject is a domesticated or livestock animal. In some embodiments, the subject is a non-mammal. In some embodiments, the non-mammal is a reptile, insect, amphibian, bird, or fish. In embodiments, the subject is a vertebrate (e.g., a mammal, a bird, a cartilaginous or bony fish, a reptile, or an amphibian). In embodiments, the subject is a human, including adults and non-adults (infants and children). In embodiments, the subject is a non-human mammal, such as a non-human primate (e.g., monkey, ape), an ungulate (e.g., cow, buffalo, bison, sheep, goat, pig, camel, llama, alpaca, deer, horse, donkey), a carnivore (e.g., dog, cat), a rodent (e.g., rat, mouse), or a lagomorph (e.g., rabbit). In embodiments, the subject is a bird, such as the avian taxa Galliformes (e.g., chickens, turkeys, pheasants, quails), Anseriformes (e.g., ducks, geese), Paleaognathae (e.g., ostriches, emus), Paleaognathae (e.g., white pigeons), or Psittaciformes (e.g., parrots). In embodiments, the subject is an invertebrate, such as an arthropod (e.g., insects, arachnids, crustaceans), nematodes, annelids, worms, or mollusks. In embodiments, the subject is an organism that is part of a symbiosis, such as part of the microbiome of an animal or plant. In embodiments, the subject is a plant such as an angiosperm (which may be dicotyledonous or monocotyledonous) or gymnosperm (e.g., conifer, cycad, gametophyte, ginkgo), fern, horsetail, club moss, or bryophyte. In embodiments, the subject is a eukaryotic alga (unicellular or multicellular). In embodiments, the subject is an agriculturally or horticulturally important plant, such as row crops, fruit-producing plants and trees, vegetables, trees, and ornamental plants, including ornamental flowers, shrubs, trees, ground covers, and turf. The plants and plant cells are of any species of interest, including dicotyledonous and monocotyledonous.Plants of interest include row crops, fruit producing plants and trees, vegetables, trees, and ornamental plants including ornamental flowers, shrubs, trees, ground covers, and turf.

[0048] Enumerated embodiments: 1. A recombinant DNA construct comprising: a heterologous promoter operably linked to a nucleic acid molecule comprising a nucleotide sequence encoding a conidial germination inhibition (CGI) factor, a CGI factor precursor, or a CGI factor fragment; The nucleotide sequence is (a) encoding at least one CGI factor, at least one CGI factor precursor, or at least one CGI factor fragment comprising an amino acid sequence having at least 80% sequence identity to at least one of SEQ ID NOs: 961 to 1920, 1957 to 2189, 2194 to 2210, 2215 to 2243, 2457 to 3361, or 5707 to 5731; or (b) a synthetic sequence of (a) having codons optimized for heterologous expression; or (c) A recombinant DNA construct encoding at least one CGI element motif. 2. The recombinant DNA construct of embodiment 2, wherein the CGI element motif comprises at least one of SEQ ID NOs: 1921-1956. 3. A recombinant DNA construct described in embodiment 1 or embodiment 2, wherein the CGI factor, CGI factor precursor, or CGI factor fragment is active and / or toxic. 4. A recombinant DNA construct described in any one of embodiments 1 to 3, wherein the recombinant DNA construct comprises (a) at least one copy of a CGI factor, (b) at least one copy of each of two or more CGI factors, (c) at least one CGI factor precursor, (d) at least one CGI factor fragment, (e) at least one CGI factor motif, or (f) any combination of (a) to (e). 5. A recombinant DNA construct according to any one of embodiments 1 to 4, wherein the heterologous promoter is a bacterial promoter, a fungal promoter, an algal promoter, an animal promoter, or a plant promoter. 6. A recombinant DNA construct according to any one of embodiments 1 to 5, wherein the heterologous promoter is a promoter capable of being expressed in a plant. 7. The recombinant DNA construct of embodiment 6, wherein the plant-expressible promoter is selected from the group of promoters consisting of ubiquitin promoter, cestrum yellow virus promoter, corn TrpA promoter, OsMADS 6 promoter, maize H3 histone promoter, corn sucrose synthetase 1 promoter, corn alcohol dehydrogenase 1 promoter, corn heat shock protein promoter, maize mtl promoter, endo small subunit RuBP carboxylase promoter, rice actin promoter, rice cyclophilin promoter, Ti plasmid mannopine synthase promoter, Ti plasmid nopaline synthase promoter, petunia chalcone isomerase promoter, bean glycine-rich protein 1 promoter, potato patatin promoter, lectin promoter, CaMV 35S promoter, and S-E9 small subunit RuBP carboxylase promoter. 8. A recombinant DNA construct described in any one of embodiments 1 to 7, wherein the recombinant DNA construct further comprises a nucleotide sequence encoding at least one secretory signal peptide functional in the cell. 9. A method for providing an organism with resistance to a fungal pathogen of the organism, comprising expressing in a cell of the organism a recombinant DNA construct described in any one of embodiments 1 to 8, wherein a heterologous promoter functions in the organism. 10. The method of embodiment 9, wherein the nucleotide sequence encoding a CGI factor, a CGI factor precursor, a CGI factor fragment, or a CGI factor motif is not present in the genome of the fungal pathogen. 11. The method of embodiment 9, wherein the recombinant DNA construct is introduced into cells of the organism by (a) transfection, (b) inheritance from a parent cell, or (c) fusion with a donor cell containing the recombinant DNA construct. 12. The method of embodiment 9, wherein the organism is a plant and the recombinant DNA construct is provided to the plant by (a) transformation, or (b) inheritance from at least one parent plant that contained the recombinant DNA construct. 13. The method of embodiment 12, wherein the plant is selected from the group consisting of a corn plant, a soybean plant, a wheat plant, a rice plant, a cotton plant, a potato plant, a tomato plant, a Brassica spp. plant, and a sugar beet plant. 14. A CGI factor, a CGI factor precursor, a CGI factor fragment, or a CGI factor motif encoded by a recombinant DNA construct described in any one of embodiments 1 to 8. 15. An antifungal or fungicidal composition comprising a CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif described in embodiment 14 and an agriculturally acceptable carrier. 16. The antifungal or fungicidal composition according to embodiment 15, wherein the composition is formulated as one of a seed treatment, a foliar spray treatment, a foliar dip treatment, a ready-to-use (RTU) formulation, a produce coating, a suspension concentrate, a tank mix, an aerosol, a root dip, a dip, a spray, a soil treatment, an irrigation formulation, or a sprinkler formulation. 17. The antifungal or fungicidal composition of embodiment 15, wherein the agriculturally acceptable carrier comprises a solid carrier, a liquid carrier, a gel carrier, a suspension, or an emulsion. 18. The antifungal or fungicidal composition of embodiment 15, wherein the agriculturally acceptable carrier comprises one or more of an adjuvant, an inactive ingredient, a dispersant, a surfactant, a tackifier, a binder, or a stabilizer. 19. A recombinant vector comprising the recombinant DNA construct described in any one of embodiments 1 to 8. 20. The vector described in embodiment 19, wherein the vector comprises a left T-DNA border sequence and a right T-DNA border sequence flanking the recombinant DNA construct. 21. The vector described in embodiment 19, wherein the vector is a viral vector. 22. A method for providing an organism with resistance to a fungal pathogen, the method comprising contacting the organism with a vector described in embodiment 19. 23. The method of embodiment 22, wherein the nucleotide sequence encoding a CGI factor, a CGI factor precursor, a CGI factor fragment, or a CGI factor motif is not present in the genome of the fungal pathogen. 24. An RNA transcript obtained from transcription of a recombinant DNA construct described in any one of embodiments 1 to 8. 25. A transgenic cell comprising the recombinant vector described in embodiment 19. 26. The transgenic cell of embodiment 25, wherein the cell is selected from a bacterial cell, a fungal cell, an algae cell, an animal cell, or a plant cell. 27. The transgenic cell of embodiment 26, wherein the transgenic cell is a plant cell. 28. The transgenic cell of embodiment 27, wherein the plant cell is a dicotyledonous plant cell. 29. The transgenic cell of embodiment 28, wherein the dicotyledonous plant cell is selected from the group consisting of a soybean cell, a sunflower cell, a tomato cell, a Brassica cell, a cotton cell, a sugar beet cell, and a tobacco cell. 30. The transgenic cell of embodiment 27, wherein the plant cell is a monocotyledonous plant cell. 31. The transgenic cell of embodiment 30, wherein the monocotyledonous plant cell is selected from the group consisting of a barley cell, a corn cell, an oat cell, a rice cell, a sorghum cell, a sugarcane cell, and a wheat cell. 32. A transgenic cell described in any one of embodiments 25 to 31, wherein the CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is (a) transiently expressed or (b) stably expressed. 33. A method for providing an organism with resistance to a fungal pathogen of the organism, comprising contacting the organism with a cell described in embodiment 25. 34. The method of embodiment 33, wherein the nucleotide sequence encoding a CGI factor, a CGI factor precursor, a CGI factor fragment, or a CGI factor motif is not present in the genome of the fungal pathogen. 35. A transgenic plant comprising the transgenic plant cell of embodiment 27. 36. The transgenic plant of embodiment 35, wherein the transgenic plant is a dicotyledonous plant. 37. The transgenic plant of embodiment 36, wherein the dicotyledonous plant is selected from the group consisting of a soybean plant, a sunflower plant, a tomato plant, a Brassica plant, a cotton plant, a sugar beet plant, or a tobacco plant. 38. The transgenic plant of embodiment 35, wherein the transgenic plant is a monocotyledonous plant. 39. The transgenic plant of embodiment 38, wherein the monocotyledonous plant is selected from the group consisting of a barley plant, a corn plant, an oat plant, a rice plant, a sorghum plant, a sugarcane plant, and a wheat plant. 40. The transgenic plant of embodiment 35, wherein the plant has improved resistance to fungal pathogens compared to a control plant not comprising the transgenic plant cells. 41. The transgenic plant of embodiment 39, wherein the fungal pathogen is one of Aspergillus spp.; Magnaporthe oryzae; Botrytis cinerea; Puccinia spp.; Fusarium graminearum; Fusarium oxysporum; Blumeria graminis; Mycosphaerella graminicola; Colletotrichum spp.; Ustilago maydis; Melampsora lini; Phakopsora pachyrhizi; or Rhizoctonia solani. 42. A transgenic plant described in any one of embodiments 35 to 41, wherein the nucleotide sequence encoding a CGI factor, a CGI factor precursor, a CGI factor fragment, or a CGI factor motif is not present in the genome of the fungal pathogen. 43. A transgenic seed of the transgenic plant of embodiment 35, wherein the seed comprises a recombinant DNA construct. 44. An F1 progeny plant having the transgenic plant of embodiment 35 as at least one parent, the F1 progeny plant comprising a recombinant DNA construct. 45. A harvest product produced from a transgenic plant described in embodiment 35, the harvest product comprising a recombinant DNA construct. 46. ​​The harvested product of embodiment 45, wherein the harvested product is a fruit, leaf, stem, flower, root, tuber, or seed. 47. A method for producing a disease resistant plant, comprising: Introducing into a plant a recombinant DNA construct according to any one of embodiments 1 to 8, wherein the CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is expressed in the plant; The plant is edited to express a CGI factor, a CGI factor precursor, or a CGI fragment comprising an amino acid sequence having at least 80% sequence identity to at least one of SEQ ID NOs: 961 to 1920, 1957 to 2189, 2194 to 2210, 2215 to 2243, 2457 to 3361, or 5707 to 5731; or Plants can be edited to express the CGI factor motif. thereby producing a disease resistant transgenic plant which is resistant to a disease caused by a fungus or oomycete. 48. The method of embodiment 47, wherein the CGI factor motif comprises at least one of SEQ ID NOs: 1921 to 1956. 49. The method of embodiment 47 or embodiment 48, wherein the CGI factor, CGI factor precursor, or CGI factor fragment inhibits the growth of and / or is toxic to fungi or oomycetes. 50. The method of any one of embodiments 47 to 49, wherein editing the plant is performed using zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), oligonucleotide-directed mutagenesis (ODM), or clustered regularly interspaced short palindromic repeats (CRISPR) / Cas nucleases. 51. A method according to any one of embodiments 47 to 49, wherein the introducing step is achieved by (a) transforming the plant, or (b) crossing a first plant containing the recombinant DNA construct with a second plant. 52. The method of any one of embodiments 47 to 49, wherein the introducing step comprises transforming the plant, and wherein transforming the plant comprises bacterial-mediated transformation, microprojectile-mediated transformation, sonication, electroporation, nanoparticle-mediated transformation, or liposome- or spheroplast-mediated vector delivery. 53. The method of any one of embodiments 47 to 52, wherein the plant is a corn plant, a soybean plant, a wheat plant, a rice plant, a cotton plant, a potato plant, a tomato plant, a Brassica plant, or a sugar beet plant. 54. A method for controlling a fungal pathogen, comprising delivering to the fungal pathogen or its environment an effective amount of a composition comprising a CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif described in embodiment 14. 55. An antifungal composition comprising: (a) an effective amount of at least one conidial germination inhibition (CGI) factor, CGI factor precursor, CGI factor fragment, or CGI factor motif, (i) comprising a polypeptide comprising an amino acid sequence having at least 80% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 961 to 1920, 1957 to 2189, 2194 to 2210, 2215 to 2243, 2457 to 3361, or 5707 to 5731; or (ii) at least one CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif, comprising a polypeptide comprising an amino acid sequence of a CGI factor motif; (b) a carrier. 56. An antifungal composition described in embodiment 53, wherein the CGI factor motif includes at least one of SEQ ID NOs: 1921 to 1956. 57. An antifungal composition described in embodiment 55 or embodiment 56, wherein the CGI factor, CGI factor precursor, or CGI factor fragment inhibits the growth of and / or is toxic to fungi or oomycetes. 58. An antifungal composition described in any one of embodiments 55 to 57, wherein the carrier is selected from an agriculturally acceptable carrier or a pharma- ceutical acceptable carrier. 59. An antifungal composition described in any one of embodiments 55 to 58, wherein the composition is formulated as a liquid, gel, emulsion, suspension, encapsulant, solid, powder, coating, spray, soil drench, granule, seed coat, or bait. 60. A method for providing an organism with resistance to a fungal pathogen of the organism, comprising contacting the organism with an antifungal composition described in any one of embodiments 55 to 59. 61. The method of embodiment 60, wherein the nucleotide sequence encoding a CGI factor, a CGI factor precursor, a CGI factor fragment, or a CGI factor motif is not present in the genome of the fungal pathogen. 62. A method for controlling a fungal pathogen, the method comprising: A method comprising applying to a fungal pathogen or a locus containing a fungal pathogen a composition comprising a conidial germination inhibitor (CGI) factor, a CGI factor precursor, a CGI factor fragment, or a CGI factor motif derived from at least one of the fungal pathogen, a fungus of the same genus as the pathogen, a fungus of a different genus from the fungal pathogen, or a mixture thereof. 63. The method of embodiment 62, wherein the CGI factor has an amino acid sequence selected from the group consisting of SEQ ID NOs: 961 to 1920, 1957 to 2189, 2194 to 2210, 2215 to 2243, 2457 to 3361, or 5707 to 5731, or an amino acid sequence having at least 80% sequence identity thereto, or the CGI factor motif includes at least one of SEQ ID NOs: 1921 to 1956. 64. The method of embodiment 62 or embodiment 63, wherein the CGI factor, CGI factor precursor, CGI factor fragment, or CGI motif is active and / or toxic. 65. A plant having a genome that has been modified to express a heterologous DNA sequence encoding a polypeptide comprising at least one conidial germination inhibitor (CGI) factor, CGI factor precursor, CGI factor fragment, or CGI factor motif, optionally fused to at least one plant secretory signal peptide, wherein the CGI factor, CGI factor precursor, CGI factor fragment, or CGI motif inhibits conidial germination, growth, or reproduction of a fungal pathogen of the plant, and the CGI factor comprises an amino acid sequence having at least 80% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 961-1920, 1957-2189, 2194-2210, 2215-2243, 2457-3361, or 5707-5731, or the CGI motif comprises at least one of SEQ ID NOs: 1921-1956, and the plant has improved resistance to the fungal pathogen compared to a control plant that does not express the heterologous DNA sequence. 66. A plant described in embodiment 65, wherein the nucleotide sequence of at least one CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is not present in the genome of a fungal pathogen. 67. A plant according to embodiment 65 or embodiment 66, wherein the fungal pathogen is one of Aspergillus spp.; Magnaporthe oryzae; Botrytis cinerea; Puccinia spp.; Fusarium graminearum; Fusarium oxysporum; Blumeria graminis; Mycosphaerella graminicola; Colletotrichum spp.; Ustilago maydis; Melampsora lini; Phakopsora pachyrhizi; or Rhizoctonia solani. 68. A cell comprising a recombinant DNA construct for expressing a CGI factor, a CGI factor precursor, a CGI factor fragment, or a CGI factor motif, 1. A plant comprising a cell comprising a heterologous promoter that functions in the cell and is operably linked to a nucleic acid molecule comprising: (a) a nucleotide sequence encoding at least one conidial germination inhibition (CGI) factor, CGI factor precursor, CGI factor fragment, or CGI motif; and (b) a nucleotide sequence encoding at least one secretion signal peptide that functions in the cell, The CGI factor comprises an amino acid sequence having at least 80% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 961 to 1920, 1957 to 2189, 2194 to 2210, 2215 to 2243, 2457 to 3361, or 5707 to 5731, or the CGI factor motif comprises at least one of SEQ ID NOs: 1921 to 1956; A plant, wherein the nucleotide sequence encoding at least one CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif optionally contains at least one codon optimized for expression in the cell. 69. A plant described in embodiment 68, wherein the CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is active and / or toxic. 70. A plant described in embodiment 68 or embodiment 69, wherein the cell is a plant cell. 71. A plant described in embodiment 68 or embodiment 69, wherein the cell is a bacterial or fungal cell in or on the plant. 72. A plant described in any one of embodiments 68 to 71, wherein the plant has improved resistance to fungal pathogens compared to a control plant not comprising the cells. 73. The plant according to embodiment 72, wherein the fungal pathogen is one of Aspergillus spp.; Magnaporthe oryzae; Botrytis cinerea; Puccinia spp.; Fusarium graminearum; Fusarium oxysporum; Blumeria graminis; Mycosphaerella graminicola; Colletotrichum spp.; Ustilago maydis; Melampsora lini; Phakopsora pachyrhizi; or Rhizoctonia solani. 74. A plant described in any one of embodiments 68 to 73, wherein a nucleotide sequence encoding at least one CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is not present in the genome of a fungal pathogen. 75. A method for controlling fungal growth or reproduction, comprising providing to a fungus an effective amount of a composition comprising at least one conidial germination inhibitor (CGI) factor, CGI factor precursor, CGI factor fragment, or CGI factor motif, wherein the CGI factor comprises an amino acid sequence having at least 80% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 961-1920, 1957-2189, 2194-2210, 2215-2243, 2457-3361, or 5707-5731, or the CGI factor motif comprises at least one of SEQ ID NOs: 1921-1956, and the nucleotide sequence of the at least one CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is not present in the genome of the fungus. 76. The method of embodiment 75, wherein the CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is active and / or toxic. 77. The method of embodiment 75 or embodiment 76, wherein the composition is provided to the fungus by directly contacting the fungus with the composition or by delivering the composition to the environment of the fungus. 78. A method for preventing fungal growth on a surface, comprising treating the surface with an effective amount of a composition comprising at least one conidial germination inhibitor (CGI) factor, CGI factor precursor, CGI factor fragment, or CGI factor motif, wherein the CGI factor comprises an amino acid sequence having at least 80% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 961-1920, SEQ ID NOs: 1957-2189, SEQ ID NOs: 2194-2210, SEQ ID NOs: 2215-2243, SEQ ID NOs: 2457-3361, or SEQ ID NOs: 5707-5731, or the CGI factor motif comprises at least one of SEQ ID NOs: 1921-1956. 79. The method of embodiment 78, wherein the CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is active and / or toxic. 80. The method of embodiment 78 or embodiment 79, wherein the surface is a non-biological surface or the surface of a living organism. 81. A method according to any one of embodiments 78 to 80, wherein the nucleotide sequence of at least one CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is not present in the genome of a fungus. 82. A composition having antifungal properties, comprising a substrate or matrix complexed with at least one conidial germination inhibitor (CGI) factor, CGI factor precursor, CGI factor fragment, or CGI factor motif that is active and / or toxic, wherein the CGI factor comprises an amino acid sequence having at least 80% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 961-1920, SEQ ID NOs: 1957-2189, SEQ ID NOs: 2194-2210, SEQ ID NOs: 2215-2243, SEQ ID NOs: 2457-3361, or SEQ ID NOs: 5707-5731, or the CGI factor motif comprises at least one of SEQ ID NOs: 1921-1956. 83. The composition of embodiment 82, wherein the CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is active and / or toxic. 84. A composition described in embodiment 82 or embodiment 83, wherein complex formation between the substrate or matrix and at least one CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is by (a) a covalent bond, (b) a non-covalent bond, or (c) a combination of (a) and (b). 85. The composition of embodiment 84, wherein the substrate or matrix comprises a polypeptide. 86. The composition of embodiment 84 or embodiment 85, wherein the substrate or matrix comprises a self-assembling peptide. 87. A method for treating a subject having a fungal disease, comprising administering to the subject an antifungal or fungicidal composition comprising a CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif described in embodiment 13 and a pharma- ceutically acceptable carrier. 88. The method of embodiment 87, wherein the subject is a mammal. 89. The method of embodiment 88, wherein the mammal is a human. 90. The method of embodiment 88, wherein the mammal is a domestic animal or a livestock animal. 91. The method of any one of embodiments 87 to 90, wherein the fungal disease is caused by a fungal pathogen selected from the group consisting of Aspergillus, Candida, Coccidioides, Histoplasma, Cryptococcus, Pneumocystis, and Blastomyces fungi. 92. The method of any one of embodiments 87-91, wherein the fungal disease is aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, mucormycosis, mycetoma, tinea, sporotrichosis, paracoccidioidomycosis, talaromycosis, chromoblastomycosis, fusariosis, emergomycosis, scedosporiosis, or fungal meningitis. 93. The method of any one of embodiments 87-92, wherein the antifungal or fungicidal composition is administered intravenously, intramuscularly, subcutaneously, topically, orally, transdermally, intraperitoneally, intraorbitally, by implantation, by inhalation, intrathecally, intracerebroventricularly, or intranasally. EXAMPLES

[0049] Working Example The presently disclosed subject matter may be better understood by reference to the following examples, which are provided as illustrations of the invention and not as limitations thereof.

[0050] Example 1: This example describes the design of a conidial germination inhibitor (CGI) factor.

[0051] Materials and Methods A pUC plasmid was prepared for expression of the CGI peptides. The plasmid contained a T7 LacOperator promoter (SEQ ID NO: 2245) to drive transcription and translation of one or more CGI peptides. The T7 promoter was codon-optimized to drive transcription and translation of the CGI peptides. The plasmid contains, from 5' to 3', a linear polynucleotide sequence containing a 5' peptide secretion sequence, an N-terminal His tag sequence (SEQ ID NO: 2246), a protease cleavage site (SEQ ID NO: 2247), and the CGI peptide sequence. The plasmid also contained a transcription termination sequence (SEQ ID NO: 2244).

[0052] Example 2: This example describes the expression of CGI elements in bacteria.

[0053] Materials and Methods E. coli (BL21(DE3)) harboring the pUC plasmid containing the CGI element construct was cultured as previously described in Example 1. A single bacterial colony was inoculated into lysogeny (LB) medium to generate a starter culture. The starter culture was then placed in a shaker at 37°C until the optical density at 600 nm (OD600) reached 0.4-0.8. Expression of the plasmid promoter was then induced with 40-400 μM isopropyl β-d-1-thiogalactopranoside (IPTG) overnight at 37°C.

[0054] Example 3: This example describes the purification of CGI factors.

[0055] Materials and Methods Purification of recombinant peptides was performed as previously described (Nallamsetty, S., and Waugh, DS (2007) Biochem Biophys Res Commun. 364(3):639-44). A homogenizer was used at 10,000-11,000 psi to lyse the bacterial cell suspension. The lysed cell suspension was then centrifuged at 15,000×g for 30 min. The cell debris was filtered using a 0.45 mm polyethersulfone membrane and then subjected to chromatography. The supernatant was then applied to a nickel-nitrilotriacetic acid (Ni-NTA) resin column equilibrated in 50 mM sodium phosphate buffer (pH 7.7), 150 mM sodium chloride, and 25 mM imidazole. The column was washed with equilibration buffer until a stable baseline was reached. The bound fusion protein was then eluted in a linear gradient over 10 column volumes in 50 mM sodium phosphate buffer (pH 7.7), 150 mM sodium chloride and 250 mM imidazole. Protein fractions were pooled and the resulting sample was concentrated approximately 10-fold. Any additional cell debris was also precipitated by centrifugation at 5000×g for 10 min. His6-TEV protease was then added to remove the protein tag from the fusion protein and digested overnight at 41° C. Efficient cleavage was confirmed by SDS-PEGE gel analysis.

[0056] Example 4: This example illustrates the design and validation of peptide inhibitors of fungal pathogens.

[0057] Materials and Methods Conidial germination inhibitor (CGI) factor To identify new compounds and targets for killing pathogenic fungi, a series of short peptides were designed based on fungal mating pheromones. The sequences for peptides 105-119 used in this study are SEQ ID NOs: 2196-2210, respectively. The peptides were expressed and purified as described in Examples 1-3.

[0058] Conidial germination inhibition colorimetric assay Biomass was generated by inoculating Fusarium or Botrytis spores onto potato dextrose agar plates and subsequently incubating the inoculated plates in a sealed plastic box for 7 days. After incubation, the plates were rinsed with 15 mL of sterile water and a pipette was used to aspirate the water above the mycelium, bringing the conidia into suspension. 15 mL of the conidial suspension was then transferred to a Falcon tube and switched to 0.5% (w / v) D-glucose. Microconidia were quantified using a glass hemocytometer (Weber Scientific, Cat. No. 3048-11). 10 μL of the microconidial suspension was transferred to a cover slip under a glass hemocytometer platelet chamber. The number of conidia in each of the 16 square sections of the hemocytometer was counted and the average count was multiplied by 10^4 to obtain the number of conidia per mL in the original suspension.

[0059] For microconidial treatment, a stock solution of 2 mM fenpiclonil (Millipore Sigma, Cat. No. 36532) solution was prepared using 50% (w / v) ethanol in water. Peptide solutions were prepared using 50% (w / v) ethanol in water. 96-well plates (VWR, Cat. No. 734-2781) were prepared by adding treatment solutions and microconidia to each well to obtain the desired treatment concentration and 1x10^6 conidia / mL in a final volume of 150 μL per well. The volume was adjusted using potato dextrose broth (PDB; Alpha Biosciences, Cat. No. P16-126). The plates were then covered and incubated at 30°C for 18 hours and 200 rpm. Afterwards, 15 μL of Prestoblue cell viability reagent (Thermofisher Scientific, Cat. No. A13262) was added to each well and the plates were further incubated for 7 hours. Fluorescence at 590 nm emission after excitation at 560 nm was then recorded using a spectrophotometer (BioTek Synergy H1 microplate reader, Fischer Scientific, Cat. No. 11-120-533).

[0060] result Peptides 105-119 (SEQ ID NOs: 2196-2210, respectively) were prepared and evaluated for their effect on asexual reproduction of fungi. Untreated microconidia and microconidia treated with 50% (w / v) ethanol in water were used as negative controls for the conidial germination inhibition assay, while the fungicidal compound fenpiclonil was used as a positive control (Figure 1A). Figure 2A shows an exemplary layout of a 96-well plate as used in the conidial germination inhibition assay, while Figure 2B shows the validation of the resazurin-based cell viability reagent used in this study.

[0061] Treatment of Fusarium or Botrytis conidia with the candidate CGI factors resulted in inhibition of conidial germination (Figure 2A). This inhibition was concentration-dependent (Figures 2B-2C). Peptide 106, derived from the Botrytis pheromone, resulted in a reduction in Botrytis conidial germination (Figures 2D-2E). Peptide 107, derived from the Saccharomyces cerevisiae pheromone, inhibited the germination of both Botrytis and Fusarium conidia (Figures 2D-2E), with the strongest inhibition observed at a concentration of 375 μM (Figures 3 and 4).

[0062] conclusion Fungal pheromones typically promote fungal growth. Here, we demonstrate that peptides derived from fungal pheromones unexpectedly inhibit the growth of Botrytis and Fusarium. Novel CGI factors based on fungal pheromones can be applied to control fungal infections in plants.

[0063] Example 5: This example illustrates the antifungal activity of tandem CGI elements when applied to seeds.

[0064] Materials and Methods Expression and purification of tandem CGI elements A plasmid vector is prepared for tandem CGI expression. The plasmid vector contains (5' to 3'): the T7 LacOperator promoter (SEQ ID NO:2245); the Shine-Dalgarno sequence (SEQ ID NO:2251); a linear polynucleotide sequence encoding an N-terminal His tag sequence (SEQ ID NO:2246); a TEV protease cleavage tag (SEQ ID NO:2247); the first CGI peptide sequence; the P2A cleavage peptide (if not used in bacteria) or the translation initiation region (TIR; if used in bacteria) (SEQ ID NO:2252); the second CGI peptide sequence; and the T7 transcription termination sequence (SEQ ID NO:2244).

[0065] Escherichia coli (BL21(DE3)) carrying the tandem CGI plasmid is prepared as described in Example 1, and the tandem CGI elements are expressed and purified as described in Examples 2-3.

[0066] Seed treatment application The first and second peptides are produced in stoichiometric and equimolar ratios before and during purification. Corn or tomato seeds are immersed in 10 mL of CGI peptide solution in a 50 mL conical tube and incubated on a shaker for 30 minutes. The coated seeds are allowed to dry overnight in a fume hood.

[0067] result Tandem CGIs are prepared from GCI elements corresponding to peptides 105-119 as described in Example 4. The tandem CGIs prepared in this study are SEQ ID NO:1957, SEQ ID NO:1958, SEQ ID NO:1959, SEQ ID NO:1960, SEQ ID NO:1961, SEQ ID NO:1962, SEQ ID NO:1963, SEQ ID NO:1964, SEQ ID NO:1965, SEQ ID NO:1966, SEQ ID NO:1967, SEQ ID NO:1968, SEQ ID NO:1969, SEQ ID NO:1970, SEQ ID NO:1971, SEQ ID NO:1972, SEQ ID NO:1973, SEQ ID NO:1974, SEQ ID NO:1975, SEQ ID NO:1976, SEQ ID NO:1977, SEQ ID NO:1978, SEQ ID NO:1979, SEQ ID NO:1980, SEQ ID NO:1981, SEQ ID NO:1982, SEQ ID NO:1983, SEQ ID NO:1984, SEQ ID NO:1985, SEQ ID NO:1986, SEQ ID NO:1987, SEQ ID NO:1988, SEQ ID NO:1989, SEQ ID NO:1990, SEQ ID NO:1991, SEQ ID NO:1992, SEQ ID NO:1993, SEQ ID NO:1994, SEQ ID NO:1995, SEQ ID NO:1996, SEQ ID NO:1997, SEQ ID NO:1998, SEQ ID NO:1999, SEQ ID NO:1990, SEQ ID NO:1991, SEQ ID NO:1992, SEQ ID NO:1993 Column number 1981, sequence number 1982, sequence number 1983, sequence number 1984, sequence number 1985, sequence number 1986, sequence number 1987, sequence number 1988, sequence number 1989, sequence number 1990, sequence number 1991, sequence number 1992, sequence number 1993, sequence number 1994, sequence number 1995, sequence number 1996, sequence number 1997, sequence number 1998, sequence number 1999, sequence number 2000, sequence number 2001, sequence number 2002, sequence number 2003, sequence number 2004, sequence number 2005, sequence number 2006, sequence number 2007, SEQ ID NO:2008, SEQ ID NO:2009, SEQ ID NO:2010, SEQ ID NO:2011, SEQ ID NO:2012, SEQ ID NO:2013, SEQ ID NO:2014, SEQ ID NO:2015, SEQ ID NO:2016, SEQ ID NO:2017, SEQ ID NO:2018, SEQ ID NO:2019, SEQ ID NO:2020, SEQ ID NO:2021, SEQ ID NO:2022, SEQ ID NO:2023, SEQ ID NO:2024, SEQ ID NO:2025, SEQ ID NO:2026, SEQ ID NO:2027, SEQ ID NO:2028, SEQ ID NO:2029, SEQ ID NO:2030, SEQ ID NO:2031, SEQ ID NO:2032, SEQ ID NO:20 33, SEQ ID NO:2034, SEQ ID NO:2035, SEQ ID NO:2036, SEQ ID NO:2037, SEQ ID NO:2038, SEQ ID NO:2039, SEQ ID NO:2040, SEQ ID NO:2041, SEQ ID NO:2042, SEQ ID NO:2043, SEQ ID NO:2044, SEQ ID NO:2045, SEQ ID NO:2046, SEQ ID NO:2047, SEQ ID NO:2048, SEQ ID NO:2049, SEQ ID NO:2050, SEQ ID NO:2051, SEQ ID NO:2052, SEQ ID NO:2053, SEQ ID NO:2054, SEQ ID NO:2055, SEQ ID NO:2056, SEQ ID NO:2057, SEQ ID NO:2058, SEQ ID NO:2059,SEQ ID NO:2060, SEQ ID NO:2061, SEQ ID NO:2062, SEQ ID NO:2063, SEQ ID NO:2064, SEQ ID NO:2065, SEQ ID NO:2066, SEQ ID NO:2067, SEQ ID NO:2068, SEQ ID NO:2069, SEQ ID NO:2070, SEQ ID NO:2071, SEQ ID NO:2072, SEQ ID NO:2073, SEQ ID NO:2074, SEQ ID NO:2075, SEQ ID NO:2076, SEQ ID NO:2077, SEQ ID NO:2078, SEQ ID NO:2079, SEQ ID NO:2080, SEQ ID NO:2081, SEQ ID NO:2082, SEQ ID NO:2083, SEQ ID NO:2084, SEQ ID NO:2085, SEQ ID NO:2086, 87, SEQ ID NO:2088, SEQ ID NO:2089, SEQ ID NO:2090, SEQ ID NO:2091, SEQ ID NO:2092, SEQ ID NO:2093, SEQ ID NO:2094, SEQ ID NO:2095, SEQ ID NO:2096, SEQ ID NO:2097, SEQ ID NO:2098, SEQ ID NO:2099, SEQ ID NO:2100, SEQ ID NO:2101, SEQ ID NO:2102, SEQ ID NO:2103, SEQ ID NO:2104, SEQ ID NO:2105, SEQ ID NO:2106, SEQ ID NO:2107, SEQ ID NO:2108, SEQ ID NO:2109, SEQ ID NO:2110, SEQ ID NO:2111, SEQ ID NO:2112, SEQ ID NO:2113, SEQ ID NO:2114, 2115, SEQ ID NO:2116, SEQ ID NO:2117, SEQ ID NO:2118, SEQ ID NO:2119, SEQ ID NO:2120, SEQ ID NO:2121, SEQ ID NO:2122, SEQ ID NO:2123, SEQ ID NO:2124, SEQ ID NO:2125, SEQ ID NO:2126, SEQ ID NO:2127, SEQ ID NO:2128, SEQ ID NO:2129, SEQ ID NO:2130, SEQ ID NO:2131, SEQ ID NO:2132, SEQ ID NO:2133, SEQ ID NO:2134, SEQ ID NO:2135, SEQ ID NO:2136, SEQ ID NO:2137, SEQ ID NO:2138, SEQ ID NO:2139, SEQ ID NO:2140, SEQ ID NO:2141, SEQ ID NO:2142, SEQ ID NO: No. 2143, No. 2144, No. 2145, No. 2146, No. 2147, No. 2148, No. 2149, No. 2150, No. 2151, No. 2152, No. 2153, No. 2154, No. 2155, No. 2156, No. 2157, No. 2158, No. 2159, No. 2160, No. 2161, No. 2162, No. 2163, No. 2164, No. 2165, No. 2166, No. 2167, No. 2168, No. 2169, No. 2170,SEQ ID NO:2171, SEQ ID NO:2172, SEQ ID NO:2173, SEQ ID NO:2174, SEQ ID NO:2175, SEQ ID NO:2176, SEQ ID NO:2177, SEQ ID NO:2178, SEQ ID NO:2179, SEQ ID NO:2180, and / or SEQ ID NO:2181.

[0068] Example 6: This example illustrates the antifungal activity of a single CGI peptide when applied to seeds.

[0069] Materials and Methods Purification and expression of CGI peptides Prepare the CGI peptide plasmid. The plasmid contains (5' to 3'): the T7 LacOperator promoter (SEQ ID NO:2245), a Shine-Dalgarno sequence (SEQ ID NO:2251), a linear polynucleotide sequence encoding an N-terminal His tag sequence (SEQ ID NO:2246), a TEV protease cleavage tag (SEQ ID NO:2247), and a peptide sequence; and a T7 transcription termination sequence (SEQ ID NO:2244).

[0070] Escherichia coli (BL21(DE3)) carrying the CGI peptide plasmid is prepared as described in Example 1, and the tandem CGI elements are expressed and purified as described in Examples 2-3.

[0071] Seed treatment application Corn or tomato seeds are immersed in 10 mL of CGI peptide solution in a 50 mL conical tube and incubated on a shaker for 30 minutes. The coated seeds are allowed to dry overnight in a fume hood.

[0072] Example 7: This example illustrates the delivery of CGI factors into seeds.

[0073] Materials and Methods Purification and expression of CGI factors E. coli (BL21(DE3)) carrying a pUC plasmid containing the CGI factor is produced and purified as described in Examples 1-3. The CGI factor is then formulated for use as a seed treatment or plantable composition. In addition to the insecticidal minicells, the formulation can include other insecticides, surfactants, film-forming polymers, carriers, antifreeze agents, and / or formulation additives. These ingredients, taken together, provide a composition that is storage stable and suitable for use in conventional seed treating equipment such as slurry seed treating equipment, direct treating equipment, farm hopper boxes, or planter boxes.

[0074] For the seed treatment formulation, 40% CGI peptide is prepared in 3% EP / PO block copolymer, tristyrylphenol, 0.5% ethoxylate, 5% calcium salt with red dye, 0.2% silicone oil and water and incubated with rice seeds overnight under a negative flow laboratory hood.

[0075] The untreated versus treated rice seeds are then analyzed to determine the coverage of fungal growth.

[0076] Example 8: This example illustrates the application of CGI factors to post-harvest crops.

[0077] Materials and Methods Strawberries are obtained and sorted based on size. The smallest size fruits are surface sterilized by immersion in 70% ethanol for one minute. The fruits are then rinsed three times with water to remove excess water before applying the CGI factor.

[0078] For application of CGI factors, treatment solutions (CGI and control) are prepared. For each treatment condition, six strawberries are placed on a petri dish and placed in a fume hood. Each strawberry is sprayed with 2 mL of treatment solution, covering the entire fruit, including the skin. Alternatively, the fruits are immersed one by one in the treatment solution. The treated fruits are then allowed to dry for 15 minutes on the fume hood.

[0079] After strawberry treatment, a conidial suspension is prepared by rinsing a plate of Botrytis grown for 7 days with 10 mL of water. The solution is then pipetted into a tube and 50 mg of D-glucose is added. The treated strawberries are transferred to new Petri dishes in a plastic container, 3 mL of conidial suspension is added to each Petri dish, and the strawberries are gently swirled to spread the suspension over the fruit's surface. The plastic container is then covered and incubated at room temperature for 7 days. The strawberries are evaluated at the end of the incubation period to determine the effectiveness of the treatment solution compared to untreated control samples.

[0080] result Organic strawberries are at risk of fungal infection at any time after harvest. Damage can occur during shipping or packaging, which increases the fruit's susceptibility to fungal pathogens. Furthermore, tightly packed strawberries are subject to constant stress and experience temperature changes when transported from the farm to the grocery store and consumer's home. Due to the highly perishable nature of the fruit, there is a large loss in quantity and quality of organic strawberries after harvest.

[0081] To address this issue, CGI factors are applied to healthy strawberries prior to packaging, either by spraying or by dipping, to prevent fungal infection. The CGI factors remain present on the fruit and inhibit spore germination until optionally washed off by the consumer.

[0082] Example 9: This example illustrates the design and validation of peptide inhibitors of fungal pathogens.

[0083] Materials and Methods Conidial germination inhibitor (CGI) factor To identify new compounds and targets for killing pathogenic fungi, a series of short peptides were designed based on fungal mating pheromones, including SEQ ID NO:2196, SEQ ID NO:2197, SEQ ID NO:2198, SEQ ID NO:2199, SEQ ID NO:2200, SEQ ID NO:2201, SEQ ID NO:2202, SEQ ID NO:2203, SEQ ID NO:2204, SEQ ID NO:2205, SEQ ID NO:2206, SEQ ID NO:2207, SEQ ID NO:2208, SEQ ID NO:2209, SEQ ID NO:2210, SEQ ID NO:2211, SEQ ID NO:2212, SEQ ID NO:2213, and SEQ ID NO:2214 (Table 1). These peptides were peptides modified by the addition of a glycine residue at either the N-terminus or C-terminus, or tandem copies, optionally separated by one or more amino acids (e.g., a linker segment such as multiple glycine residues). The peptides were expressed and purified as described in Examples 1-3.

[0084] [Table 1]

[0085] Colorimetric Fusarium viability assay Fusarium conidial suspensions were prepared from 7-day cultures of Fusarium biomass grown on potato dextrose agar for 7 days and quantified by hemocytometer as described in Example 4. Solutions of fenpiclonil (Millipore Sigma, catalog number 36532) and individual peptides were prepared in 50% (w / v) ethanol in water and tested using the PrestoBlue™ (resazurin) viability colorimetric assay as described in Example 4.

[0086] Fusarium conidial suspension, peptide or control treatment solutions and potato dextrose broth (Alpha Biosciences, Catalog No. P16-126) were added to each well of a 96-well plate to obtain the desired treatment concentration and 1x10^6 conidia / mL in a final volume of 150 microliters per well. The plate was covered and incubated at 30°C for 18 hours and 200 rpm. 15 microliters of PrestoBlue™ cell viability reagent (Thermofisher Scientific, Catalog No. A13262) was added to each well and the plate was further incubated before measuring fluorescence at 590 nm emission with excitation at 560 nm using a spectrophotometer (BioTek Synergy H1 microplate reader, Fischer Scientific, Catalog No. 11-120-533).

[0087] Colorimetric Assay for Botrytis Viability Botrytis conidial suspensions were prepared from 7-day cultures of Botrytis cinarea (strain CBS261.71) biomass grown for 7 days on potato dextrose agar and quantified by hemocytometer as described in Example 4. Solutions of fenpiclonil (Millipore Sigma, catalogue no. 36532) and individual peptides were prepared in 50% (w / v) ethanol in water and tested using the PrestoBlue™ (resazurin) viability colorimetric assay as described in Example 4.

[0088] Botrytis conidial suspension, peptide or control treatment solutions, and potato dextrose broth (Alpha Biosciences, Catalog No. P16-126) were added to each well of a 96-well plate to obtain the desired treatment concentration and 1x10^6 conidia / mL in a final volume of 150 microliters per well. The plate was covered and incubated at 30°C for 24 hours and 200 rpm. 15 microliters of PrestoBlue™ cell viability reagent (Thermofisher Scientific, Catalog No. A13262) was added to each well, and the plate was incubated for another hour before measuring fluorescence at 590 nm emission with excitation at 560 nm using a spectrophotometer (BioTek Synergy H1 microplate reader, Fischer Scientific, Catalog No. 11-120-533).

[0089] result Colorimetric Fusarium viability assay Several separate Fusarium viability experiments were performed. In the first experiment, peptides tested for their ability to inhibit conidial germination and / or reduce fungal cell viability included the natural alpha pheromone from Fusarium sp. (WCTWKGQPCW, SEQ ID NO: 2182), the natural alpha pheromone from Botrytis sp. (WCGRPGQPC, SEQ ID NO: 2183), and the natural alpha pheromone from Saccharomyces cerevisiae (WHWLQLKPGQPMY, SEQ ID NO: 2184), as well as a synthetic peptide having the amino acid sequence WKMGQYHQLPPLW (SEQ ID NO: 2185), which was synthesized from Saccharomyces cerevisiae. The CGI peptides tested included a modified Saccharomyces cerevisiae alpha pheromone with a C-terminal glycine cap having the amino acid sequence WHWLQLKPGQPMYG (based on a reconstruction of the amino acid sequence of Saccharomyces cerevisiae alpha pheromone) and a modified Saccharomyces cerevisiae alpha pheromone with a C-terminal glycine cap having the amino acid sequence WHWLQLKPGQPMYG (SEQ ID NO: 2186). The results are shown in Figure 6A. All of the CGI peptides tested demonstrated the ability to reduce Fusarium cell viability in treated samples at a concentration of 375 micromolar compared to samples that were untreated or treated only with a 50% (w / v) ethanol carrier solution in water. Notably, in this experiment, the Saccharomyces cerevisiae alpha pheromone (SEQ ID NO:2184), as well as the synthetic peptide (SEQ ID NO:2185) and the C-terminal glycine-capped Saccharomyces cerevisiae alpha pheromone (SEQ ID NO:2186), significantly reduced Fusarium cell viability to levels nearly equal to the positive control (fenpiclonil) fungicide treatment. These results demonstrated that the alpha pheromone and its derivatives encoded in the genome of one fungal genus (Saccharomyces) are unexpectedly effective in reducing the viability of cells of a different fungal genus (Fusarium).

[0090] In a second experiment, performed similarly to the first, the same peptides were tested again at a concentration of 375 micromolar and viability was measured at a later time point (51 hours after addition of resazurin). The results are shown in FIG. 6B. Similar results were obtained, with Fusarium alpha pheromone (SEQ ID NO:2182) and Botrytis alpha pheromone (SEQ ID NO:2183) also reducing Fusarium cell viability compared to samples that were untreated or treated only with a 50% (w / v) ethanol carrier solution in water. Notably, Saccharomyces cerevisiae alpha pheromone (SEQ ID NO:2184) and synthetic peptide (SEQ ID NO:2185) also significantly reduced Fusarium cell viability to nearly the same level as the positive control (fenpiclonil) fungicide treatment. These results confirm that the alpha pheromone and its derivatives encoded in the genome of one fungal genus (Saccharomyces) are unexpectedly effective in reducing the viability of cells of a different fungal genus (Fusarium).

[0091] In a third experiment, carried out similarly to the first and second experiments, eight putative conidial germination inhibitor peptides were tested at 175 micromolar and 375 micromolar. The peptides tested also included the natural alpha pheromone from Fusarium sp. (WCTWKGQPCW, SEQ ID NO: 2182), the natural alpha pheromone from Botrytis sp. (WCGRPGQPC, SEQ ID NO: 2183), and the natural alpha pheromone from Saccharomyces cerevisiae (WHWLQLKPGQPMY, SEQ ID NO: 2184), a synthetic peptide (SEQ ID NO: 2185) and a C-terminal glycine-capped Saccharomyces cerevisiae alpha pheromone (SEQ ID NO: 2186), as well as three peptides not previously tested: a modified Saccharomyces cerevisiae alpha pheromone with an N-terminal glycine cap (SEQ ID NO: 2187). The peptides included Saccharomyces cerevisiae alpha pheromone (GWHWLQLKPGQPMY, SEQ ID NO: 2187), a peptide with the sequence of adjacent tandem copies of Saccharomyces cerevisiae alpha pheromone (WHWLQLKPGQPMYWHWLQLKPGQPMY, SEQ ID NO: 2188), and a peptide with the sequence of tandem copies of Saccharomyces cerevisiae alpha pheromone separated by four glycine-linked segments (WHWLQLKPGQPMYGGGGSWHWLQLKPGQPMY, SEQ ID NO: 2189). The results are shown in Figure 6C. The observed results were similar to those obtained in the first and second experiments. At a concentration of 375 micromolar, Fusarium alpha pheromone (SEQ ID NO: 2182) and Botrytis alpha pheromone (SEQ ID NO: 2183) also reduced Fusarium cell viability compared to samples that were untreated or treated only with a 50% (w / v) ethanol carrier solution in water; at the lower concentration of 175 micromolar, this effect was less pronounced.At 375 micromolar, Saccharomyces cerevisiae alpha pheromone (SEQ ID NO:2184) and its derivatives (SEQ ID NO:2188 and 2189) also significantly reduced Fusarium cell viability to levels similar to the positive control (fenpiclonil) fungicide treatment, but showed no significant effect on Fusarium cell viability at 175 micromolar. Notably, the longer tandem peptides derived from Saccharomyces cerevisiae alpha pheromone (tandem copies without a spacer, SEQ ID NO:2188) and (tandem copies with a spacer, SEQ ID NO:2189) were effective in reducing Fusarium cell viability to levels similar to the positive control (fenpiclonil) fungicide treatment at both 175 and 375 micromolar.

[0092] Experiments 4 and 5 were performed following a similar protocol and using the same CGI peptide as experiment 3. Results from these experiments are provided in Table 2 as the mean percent inhibition and deviation from the mean (four replicates).

[0093] [Table 2]

[0094] Colorimetric Assay for Botrytis Viability Results are provided in Table 3 as the average percent inhibition and deviation from the mean (four replicates). These results were generally similar to those observed in the Fusarium viability assay. At a concentration of 375 micromolar, Fusarium alpha pheromone (SEQ ID NO: 2182) and Saccharomyces cerevisiae alpha pheromone (SEQ ID NO: 2184) reduced Botrytis cell viability compared to samples that were untreated or treated only with a carrier solution of 50% (w / v) ethanol in water. In this experiment, Saccharomyces cerevisiae alpha pheromone (SEQ ID NO:2184) and its derivatives (SEQ ID NO:2188 and 2189) reduced Fusarium cell viability by approximately 2 / 3 of the reduction in viability obtained using the positive control (fenpiclonil) fungicide treatment. As observed in the Fusarium viability experiment, at 375 micromolar, the longer tandem peptides derived from Saccharomyces cerevisiae alpha pheromone (tandem copies without a spacer, SEQ ID NO:2188) and (tandem copies with a spacer, SEQ ID NO:2189) were the most effective peptides tested, reducing Botrytis cell viability similarly to the fenpiclonil treatment. The results confirm that the alpha pheromone and its derivatives encoded in the genome of one fungal genus (Saccharomyces) are unexpectedly effective in reducing the viability of cells of a different fungal genus (Botrytis).

[0095] [Table 3]

[0096] Example 10: This example describes novel synthetic peptide inhibitors of fungal growth or viability or novel synthetic peptide inhibitors of conidial germination. More specifically, this example describes examples of synthetic peptides designed to inhibit fungal conidial germination and / or reduce cell viability.

[0097] These synthetic peptide embodiments are synthetic peptides that include an amino acid sequence that includes the sequences of at least two different CGI peptides (e.g., alpha pheromone peptides from or encoded in different biological sources, or derivatives of these alpha pheromone peptides), optionally further including additional amino acids, such as amino acids that form a spacer or linker sequence.

[0098] Another embodiment of these synthetic peptides is a synthetic peptide that contains the sequence of at least one CGI peptide or a sequence derived from at least one CGI peptide fused to a signal peptide that functions in the cell in which the synthetic peptide is expressed. Many signal peptide sequences have been described, for example, the Tat (twin arginine translocation) signal sequence is typically an N-terminal peptide sequence that contains a consensus SRRxFLK "twin arginine" motif, which acts to translocate folded proteins containing Tat signal peptides, etc., to lipid bilayers. See also the publicly available signal peptide database at www[dot]signalpeptide[dot]de. For example, a synthetic peptide that contains a CGI peptide sequence fused to a bacterial signal peptide that functions in plant cells can be expressed in plant cells or plants. See, e.g., Moeller (2019) J. Exp. Bot., 60:3337-3335; doi:10.1093 / jxb / erp167 for the bacterial signal peptide having the sequence MVKVKCYVLFTALLSSLCAYG (SEQ ID NO: 2195). Signal peptides are also useful for directing proteins to specific organelles, see, e.g., the experimentally determined and computationally predicted signal peptides disclosed in the Spdb signal peptide database publicly available at proline[dot]bic[dot]nus[dot]edu[dot]sg / spdb.

[0099] Another embodiment of these synthetic peptides is a synthetic peptide that comprises the sequence of at least one CGI peptide fused to a cell membrane penetrating peptide (CPP), or a sequence derived from at least one CGI peptide. Several hundred CPP sequences have been described, see for example the CPPsite, a public database of cell membrane penetrating peptides at crdd[dot]osdd[dot]net / raghava / cppsite / . An example of a commonly used CPP sequence is a poly-arginine sequence, e.g., octoarginine or nonoarginine, which can be fused to the C-terminus of a CGI peptide.

[0100] Another embodiment of these synthetic peptides is a synthetic peptide that includes the sequence of, or a sequence derived from, at least one CGI peptide fused or conjugated to a self-assembling peptide. In some embodiments, the self-assembling peptide is (M)(YEYK) n YEY (SEQ ID NO: 2194), where n=3 or n is 3-10, methionine is an optional amino acid at the terminal, and the self-assembling peptide is covalently or non-covalently linked to one or more CGI peptides (see, e.g., Miki et al. 2021 Nature Communications, 21:3412, DOI: 10.1038 / s41467-021-23794-6). In embodiments, the self-assembling peptide is fused to the N-terminus of the CGI peptide or to an internal site (e.g., in a linker peptide sequence linking two CGI peptides). In embodiments, the self-assembling peptide / CGI fusion or complex forms particles or structures (e.g., gels or sheets or fibers) with antifungal properties and can be formulated (e.g., paints, coatings, films, fabrics, etc.) and applied to biological or non-biological substrates or matrices (e.g., plant tissue surfaces, seeds, harvested plant parts, food, wood, plaster, inorganic building materials) to protect against fungal infestation or growth or damage.

[0101] Combinations of the above embodiments are also contemplated. For example, a synthetic peptide inhibitor of fungal growth or viability can include copies of two or more different CGI peptides (e.g., alpha pheromone peptides from different biological sources or encoded in different genomic sources, or derivatives of these alpha pheromone peptides), where the CGI peptides are linked with an amino acid binding sequence (e.g., glycine residues) and a poly-arginine CPP sequence is fused to the C-terminus of the synthetic peptide. These synthetic peptide embodiments optionally further include additional amino acids, such as amino acids forming a spacer or linker sequence, or additional amino acids located adjacent to the alpha pheromone sequence (e.g., a "cap" of one or more amino acids at the N-terminus or C-terminus of an individual alpha pheromone sequence or of the peptide molecule as a whole).

[0102] Non-limiting examples of these synthetic peptides are provided in Table 4.

[0103] [Table 4]

[0104] [Table 5]

[0105] Example 11: This example describes novel synthetic fusion peptides that include at least one signal peptide and at least one CGI peptide. In embodiments, one or more amino acid linkers are included in the fusion peptide, for example, linking a signal peptide to an adjacent CGI peptide, or in a fusion peptide containing two or more CGI peptides linking one CGI peptide to another CGI peptide. For economical use, the amino acid linker is relatively short, for example, 10 or fewer amino acids. In embodiments, the signal peptide is cleaved from the CGI peptide in vivo. These fusion peptide sequences are useful for expression of fusion peptides or CGI peptides in eukaryotic cells, such as, for example, plant cells. Related embodiments include eukaryotic cells and organisms (e.g., plant cells or tissues or intact plants) that transiently or stably express one or more CGI peptides or CGI peptide derivatives, such as these synthetic fusion peptides. These synthetic fusion peptides are useful for inhibiting fungal conidial germination and / or reducing cell viability.

[0106] Table 5 provides non-limiting examples of synthetic fusion peptides comprising at least one signal peptide and at least one CGI peptide, and optionally one or more amino acid linkers. These fusion peptides comprise various combinations of at least one CGI peptide with the PR1 signal sequence MGFVLFSQLPSFLLVSTLLLFLVISHSCRA (SEQ ID NO: 5699) or with the GRP signal sequence MATTKHLALAILVLLSIGMTTSA (SEQ ID NO: 5700), and optionally further comprise an amino acid linker of 1-9 amino acids (shown as underlined text in Table 5).

[0107] [Table 6]

[0108] [Table 7]

[0109] Example 12 This example describes the identification of a conidial germination inhibition (CGI) factor sequence.

[0110] Additional conidial germination inhibition (CGI) factor sequences have been identified from ascomycete fungi, and the CGI factor amino acid sequences are provided herein as SEQ ID NOs: 2457-3361. Additionally, at least one corresponding genomic DNA sequence has been identified for each of the CGI factors, and is provided herein as SEQ ID NOs: 3362-5698. The ascomycete fungal genomes were included in the genomes of fungal species known to be pathogenic to animals, e.g., invertebrates (such as arthropods, nematodes, annelids, worms, mollusks, etc.) and vertebrates (such as mammals, birds, cartilaginous or bony fish, reptiles, or amphibians). In some embodiments, the fungal genome is of a fungal species that is pathogenic in birds, e.g., domestic poultry and waterfowl. In some embodiments, the fungal genome is of a fungal species that is pathogenic in mammals, such as domestic mammals (dogs, cats, domestic ungulates, and lagomorphs), non-human primates, or humans. In certain embodiments, the fungal genome is of a fungal species that is pathogenic in humans, including adults and non-adults (infants and children).

[0111] [Table 8]

[0112] [Table 9]

[0113] [Table 10]

[0114] [Table 11]

[0115]

Table 12

[0116]

Table 13

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Table 14

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Table 15

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[0198] [Table 95]

[0199] [Table 96]

[0200] [Table 97]

[0201] [Table 98]

[0202] [Table 99]

[0203] [Table 100]

[0204] Example 13 This example describes the expression of at least one conidial germination inhibitor (CGI) factor in a plant cell. More specifically, this example illustrates bacterial-mediated transfection into a plant of various DNA constructs encoding at least one CGI factor peptide, resulting in transient expression of the CGI factor peptide.

[0205] An expression cassette (construct "HD6") was designed to contain a Zea mays ubiquitin 10 promoter operably linked to and driving expression of a coding sequence encoding a secretory signal peptide ("GRP") fused to DNA encoding a synthetic CGI element "HH38" (a dimer of Saccharomyces cerevisiae alpha pheromone with a GGGG linker, having the sequence WHWLQLKPGQPMYGGGGSWHWLQLKPGQPMY, SEQ ID NO: 2189), operably linked to a NOS terminator. Variants of this expression cassette contained additional elements. See Table 7. Construct "HD7" added a FLAG tag and the fluorescent dye mCherry for immunogenicity detection. Construct "HD8" also contained a FLAG tag and mCherry fluorescent dye, and further contained an SV40 nuclear localization signal ("NLS") in place of the GRP secretory signal peptide. Finally, construct "HD9" was a control plasmid similar to HD8 but lacking the DNA encoding the CGI element HH38. See Table 7 for a description of the plasmids.

[0206] [Table 101]

[0207] Individual expression cassettes were inserted into the Ti plasmid pMP90 flanked by T-DNA right and left border sequences, providing plasmids pHD6 to pHD9, respectively. The appropriate Agrobacterium tumefaciens strain GV3101 was used for transient transformation of the resulting plasmids into Nicotiana benthamiana via leaf infiltration method. Leaf tissue from transiently transformed plants was sampled two days after infiltration for protein extraction and analyzed using Coomassie brilliant blue staining and Western blot using mouse or rabbit anti-FLAG antibodies. Coomassie staining showed the presence of peptides with the correct molecular weights in total protein extracted from leaves infiltrated with HD6, HD7, HD8, and HD9 constructs, indicating possible protein expression in these leaves. To further characterize the protein bands, Western blot analysis was performed using anti-FLAG antibody and positive bands of the correct size were observed as expected for total protein extracted from leaves infiltrated with the HD7, HD8, and HD9 constructs, as well as for protein extracted from apoplastic fluid from leaves infiltrated with the HD7 construct containing the GRP secretion signal or the HD9 construct containing the P2A cleavage sequence.

[0208] Leaf tissue from transiently transformed plants was also sampled 2 days after infiltration and subjected to fluorescence imaging at 10x magnification using an Olympus epifluorescence microscope (RFP / Cy3 channel). No fluorescence was observed in the selected channel in tissue from leaves infiltrated with HD6, a negative control construct lacking mCherry. Diffuse mCherry fluorescence was observed in tissue from leaves infiltrated with the HD7 construct, suggesting that the mCherry-tagged HH38 CGI peptide was secreted. Punctate fluorescent signals indicating nuclear localization of mCherry were observed in tissue from leaves infiltrated with the HD9 construct, which contains a nuclear localization signal fused to the mCherry reporter.

[0209] Example 14 This example illustrates a method for controlling a fungal pathogen, comprising applying to a location that contains or will be exposed to a fungal pathogen a composition comprising at least one conidial germination inhibitor (CGI) factor, CGI factor precursor, CGI factor fragment, or CGI factor motif derived from at least one of the fungal pathogen, a fungus of the same genus as the fungal pathogen, a fungus of a different genus from the fungal pathogen, or a mixture thereof. This example further illustrates providing resistance to a fungal pathogen in an organism, comprising contacting the organism with an effective amount of an antifungal composition comprising at least one CGI factor, and optionally, the amino acid sequence of the CGI factor is not the amino acid sequence of an alpha pheromone naturally expressed by the fungal pathogen, or the nucleotide sequence encoding the CGI factor is not present in the genome of the fungal pathogen. More specifically, this example shows that topical application of an antifungal CGI factor-containing composition to the leaves of a plant (Nicotiana benthamiana) effectively reduces or prevents symptoms of infection by a fungal pathogen (Botrytis cinerea). In this example, the antifungal CGI factor-containing composition includes a synthetic CGI factor "HH38," which has the amino acid sequence WHWLQLKPGQPMYGGGGSWHWLQLKPGQPMY (sequence number 2189) and is a homodimer of the natural Saccharomyces cerevisiae alpha pheromone WHWLQLKPGQPMY (sequence number 2184) with an appended GGGG linker, i.e., the synthetic CGI factor "HH38" has an amino acid sequence that is different from the alpha pheromone WCGRPGQPC (sequence number 2183) naturally expressed by the fungal pathogen Botrytis cinerea.

[0210] In one experiment, leaves of approximately the same age were excised from healthy Nicotiana benthamiana plants and the petioles were placed on plates containing plain agar. The leaves were visually divided into quarters. Each quadrant received a drop of 10 microliters of Botrytis cinerea conidial suspension (3.2E+05 conidia / mL in 10% white grape juice in water) followed by 100 microliters of a given treatment solution (or nothing added as a control), and three leaves were used per treatment condition: 5 mM 2-(N-morpholino)ethanesulfonic acid (MES) buffer; 275 micromolar CGI factor "HH38" (SEQ ID NO: 2189) in 5 mM MES buffer; 275 micromolar fenpiclonil (4-(2,3-dichlorophenyl)-1H-pyrrole-3-carbonitrile, a phenylpyrrole fungicide) in 50% ethanol; and 50%. Plates were covered, placed in a humidified secondary container, and incubated in a growth chamber under a 14-hour light (20°C):10-hour dark (18°C) cycle. After 11 days, the fungal lesions on the leaves were photographed and measured manually using a ruler. The leaves were then destained in 70% ethanol for 48 hours with ethanol changes at 24 hours, rehydrated in water for at least 1 hour, photographed, and the fungal lesions were quantified using ImageJ software (see imagej[dot]nih[dot]gov / ij / ). Under these experimental conditions, fenpiclonil was observed to be phytotoxic and tissue necrosis was observed at the treatment sites, therefore this treatment and the corresponding ethanol control were excluded from the analysis. The results for the control, MES, and CGI factor peptide HH38 are provided in Table 8 and Figure 7. The majority (10 / 12) of leaf quadrants inoculated with 10 microliters of Botrytis cinerea inoculum developed small (approximately 1 / 3 centimeter in diameter) fungal lesions at the inoculation site, indicating that this tissue was generally susceptible to B. cineria, although the small amount of fluid applied to these quadrants likely limited the size of the lesions.Leaf quadrants inoculated with B. cinerea and treated with 100 microliters of treatment solution (MES buffer or HH38 in MES buffer) had relatively large areas wet with liquid. All of the leaf quadrants treated with 5 mM MES buffer developed large (average 1.72 cm wide) fungal lesions characterized by gray to black fungal growth. In contrast, only one of 12 leaf quadrants treated with 375 micromolar CGI factor HH38 did not develop any measurable fungal lesions. These data indicate that topical application of CGI factor HH38 (SEQ ID NO: 2189) effectively inhibited the growth of Botrytis cinerea on Nicotiana benthamiana leaves. These results demonstrate that antifungal compositions containing a CGI factor effectively inhibit the growth of a fungal pathogen on or within an organism, where the amino acid sequence of the CGI factor is not the amino acid sequence of an alpha pheromone naturally expressed by the fungal pathogen, or the nucleotide sequence encoding the CGI factor is not present in the genome of the fungal pathogen.

[0211] [Table 102]

[0212] A second experiment to test the ability of CGI Factor ("HH38") (SEQ ID NO: 2189) to reduce or prevent symptoms of infection by Botrytis cinerea in Nicotiana benthamiana was conducted using a similar methodology, except that the B. cinerea inoculum (3.2E+05 conidia / mL in 10% white grape juice in water) was premixed with an equal volume of a treatment solution selected from 10% diluted white grape juice in water (as an untreated control), 5 mM MES buffer, 375 mM CGI Factor HH38 in 2% DMSO (v / v) in 5 mM MES buffer, and 2% DMSO (v / v) in water. Twenty microliters of a given treatment mixture was pipetted onto leaf quadrants (12 quadrants in total for three replicate leaves). Growth was continued for 7 days in a growth chamber. After incubation, the leaves were photographed, destained in 70% ethanol, photographed again, and the area of ​​fungal lesions was quantified using ImageJ software. In this experiment, fungal lesions in leaf quadrants treated with CGI factor HH38 peptide were 44% smaller than untreated (diluted grape juice) controls, a difference that was statistically significant using an unpaired t-test. Fungal lesions in the HH38 treatment were observed to be 39% smaller than those in the 2% DMSO treatment and 19% smaller than the 5 mM MES treatment, although this was not to a statistically significant extent using an unpaired t-test. These data indicate that topical application of synthetic CGI factor HH38 (sequence number 2189) inhibited the growth of Botrytis cinerea on Nicotiana benthamiana leaves to a statistically significant extent.

[0213] Example 15 This example provides examples of synthetic antifungal peptides having amino acid sequences derived from those of naturally occurring CGI factor peptides, and further including additional amino acids to provide desired functionality. More specifically, this example describes the antifungal activity of a synthetic CGI factor peptide having the amino acid sequence of Saccharomyces cerevisiae alpha pheromone (WHWLQLKPGQPMY, SEQ ID NO:2184) fused at its C-terminus to an octaarginine cell penetrating peptide (CPP) sequence, WHWLQLKPGQPMYRRRRRRRR (SEQ ID NO:2240).Other embodiments of the synthetic antifungal peptides include those having at their C-terminus a polyarginine CPP sequence, a polylysine CPP sequence, a Tat basic domain sequence (RKKRRQRRR, SEQ ID NO: 5736), a BP100 CPP sequence (KKLFKKILKYL, SEQ ID NO: 5737), a D-R9 CPP sequence (rrrrrrrrr (D type), SEQ ID NO: 5738), a KLA10 CPP sequence (KALKKLLAKWLAAAKALL, SEQ ID NO: 5739), a dhvar5 CPP sequence (LLLFLLKKRKKRKY, SEQ ID NO: 5740), a HPV33L2-445 / 467 CPP sequence (SYFILRRRRKRFPYFFTDVRVAA, SEQ ID NO: 5741), a Crot(27-29) derivative (2) CPP sequence (KMDCRWRWKCCKK, SEQ ID NO: 5742), a CyLoP-1 CPP sequence (CRWRWKCCKK, SEQ ID NO: 5743), a M511 The CPP sequence (FLGKKFKKYFLQLLK, SEQ ID NO: 5744), E162 CPP sequence (KTVLLRKLLKLLVRKI, SEQ ID NO: 5745), MG2d CPP sequence (GIGKFLHSAKKWGKAFVGQIMNC, SEQ ID NO: 5746), or another CPP sequence (e.g., publicly available at the CPP site, crdd[dot]osdd[dot]net / raghava / cppsite / , or available from Numata et al. (2018) Scientific Reports, 8:10966, DOI:10.1038 / s41598-018-29298-6)) is fused to a cell-penetrating peptide sequence (e.g., a sequence selected from the group consisting of SEQ ID NOs: 961-1920, SEQ ID NOs: 1957-2189, SEQ ID NOs: 2194-2210, SEQ ID NOs: 2215-2243, SEQ ID NOs: 2457-3361, and SEQ ID NOs: 5707-5731).

[0214] Several CGI factor peptides were synthesized and screened against a panel of several fungal pathogens. The pathogens were grown in modified RPMI medium at 25 degrees Celsius (see Vicente et al. (2009) Mycol. Res., 113:754-757, DOI: 10.1016 / j.mycres.2009.02.011). The incubation time varied according to the species: 24 hours for Fusarium culmorum, 22 hours for Fusarium graminearum, 7 days for Phytophthora infestans, and 5 days for Zymoseptoria tritici. Peptides were dissolved in DMSO and diluted in modified RPMI medium, but when attempting to dissolve these peptides in fungal medium, precipitation was observed for many peptides and therefore these experiments were not considered. Nevertheless, synthetic CGI factor peptides containing the octaarginine CPP sequence (SEQ ID NO: 2240) have been shown to inhibit the growth of important plant pathogens Fusarium culmorum (the fungal causal agent of several "wither" and "rot" diseases of various dicotyledonous and monocotyledonous plants, including cereals; 24 hour incubation), Fusarium graminearum (the anamorph of Gibberella zeae and the fungal causal agent of fusarium head blight in wheat and barley, and the fungal causal agent of maize ear and stalk rot; 22 hour incubation), Phytophthora infestans (the fungal causal agent of fusarium head blight in wheat and barley, and the fungal causal agent of maize ear and stalk rot; 22 hour incubation), and Fusarium graminearum (the fungal causal agent of fusarium head blight in wheat and barley, and the fungal causal agent of maize ear and stalk rot; 22 hour incubation). We observed strong inhibition (≥50% inhibition vs. control) of Septoria infestans (the "fungal" causal agent of tomato late blight and potato blight; 7 days incubation), and Zymoseptoria tritici (Septoria tritici, the fungal causal agent of Septoria leaf blight in wheat; 5 days incubation).Accordingly, related embodiments include Fusarium culmorum, Fusarium graminearum, Phytophthora infestans, and Zymoseptoria trichii. tritici, by providing to a plant infected with or at risk of infection by one or more of these pathogens at least one synthetic polypeptide having a sequence that includes at least one CGI peptide or one or more CGI factor peptide sequences, and a cell penetrating peptide sequence, particular embodiments of the synthetic polypeptide include a polypeptide having a sequence of a CGI factor peptide selected from SEQ ID NOs: 961-1920, 1957-2189, 2194-2210, 2215-2243, 2457-3361, and 5707-5731 fused at its C-terminus to a polyarginine CPP sequence, such as octoarginine or nonoarginine.

[0215] Example 16 This example illustrates a method for reducing or inhibiting the growth of a fungal pathogen by contacting the fungal pathogen with a composition comprising at least one conidial germination inhibitor (CGI) factor, CGI factor precursor, CGI factor fragment, or CGI factor motif derived from at least one of the fungal pathogen, a fungus of the same genus as the fungal pathogen, a fungus of a different genus from the fungal pathogen, or a mixture thereof.

[0216] Experiments to test the ability of CGI factors to inhibit the growth of or kill fungal pathogens were carried out using the natural Botrytis cinerea alpha pheromone WCGRPGQPC (SEQ ID NO: 2183), the natural Saccharomyces cerevisiae alpha pheromone WHWLQLKPGQPMY (SEQ ID NO: 2184), and the synthetic CGI factor "HH38" (SEQ ID NO: 2189, a homodimer of the natural Saccharomyces cerevisiae alpha pheromone with an appended GGGG linker) having the amino acid sequence WHWLQLKPGQPMYGGGGSWHWLQLKPGQPMY. The CGI factor peptides were synthesized and provided as lyophilized powders, and for screening the peptides were dissolved in DMSO and diluted to a 9375 micromolar stock solution in 50% DMSO.

[0217] The fungal species and strains selected for testing are listed in Table 9. They are mycelium forming or grow as yeasts. Fungal stocks were initially grown on appropriate regeneration medium at 30 degrees Celsius and then on assay medium at 37 degrees Celsius.

[0218] [Table 103]

[0219] The screening process was carried out as a broth microdilution assay in 96-well plates, following the guidelines provided by the Clinical and Laboratory Standards Institute (CLSI, clsi[dot]org) or a modification of the standardized method of the German Institute for Standardization (DIN, din[dot]de). The inoculum titers for the test plates were 0.5-5x10^4 for fungal spores and 1-2.5x10^3 for yeast cells. Mycelium formation was often observed to be unevenly distributed throughout the wells, therefore fungal growth was further evaluated by microscopic examination.

[0220] Preliminary results for the three peptides were as follows: no inhibition of growth of Aspergillus fumigatus, Aspergillus flavus, Fusarium oxysporum, Mucor circinelloides f. janssenii, or Rhizomucor miehei was observed after 3 days of incubation with either Botrytis alpha pheromone (SEQ ID NO: 2183) or Saccharomyces alpha pheromone (SEQ ID NO: 2184) at 375 or 187.5 micromolar concentrations, but the synthetic CGI factor "HH38" (SEQ ID NO: 2189) could induce changes in growth patterns. No inhibition of growth of Candida albicans, Candida parapsilosis, or Candida auris was observed after 1 day of incubation with any of the three peptides at 375 or 187.5 micromolar. Both Botrytis alpha pheromone (SEQ ID NO: 2183) and Saccharomyces alpha pheromone (SEQ ID NO: 2184) at a concentration of 375 micromolar were observed to reduce the growth of Cryptococcus neoformans after 2 days of incubation, and the synthetic CGI factor "HH38" (SEQ ID NO: 2189) at 375 micromolar altered the growth pattern of this species. As these are preliminary results, the assays are being further refined to allow for the investigation of CGI peptide antifungal activity across a range of human and animal fungal pathogens.

[0221] Example 17 This example illustrates a method for reducing or inhibiting the growth of a fungal pathogen by contacting the fungal pathogen with a composition comprising at least one conidial germination inhibitor (CGI) factor, CGI factor precursor, CGI factor fragment, or CGI factor motif derived from at least one of the fungal pathogen, a fungus of the same genus as the fungal pathogen, a fungus of a different genus from the fungal pathogen, or a mixture thereof. More specifically, this example illustrates the use of a live cell imaging system to examine the effects of a putative CGI factor peptide.

[0222] The oCelloScope™ (BioSense Solutions ApS, Farum, DK) optical detection system was used to image 96-well plates containing Fusarium proliferatum conidia grown for 22 hours in 30% diluted potato dextrose broth. Fungal growth was determined using the "Segmentation and Extraction of Surface Area" ("SESA") algorithm (see Fredborg et al. (2013) J. Clinical Microbiol., 51:2047 - 2053; DOI:10.1128 / JCM.00440-13). Ten CGI factor peptides were tested, including three naturally occurring alpha pheromone peptides and seven synthetic CGI factors with amino acid sequences derived from one or more naturally occurring alpha pheromone peptide sequences, as follows: (1) "HH1", Fusarium graminearum alpha pheromone (WCTWKGQPCW, SEQ ID NO: 2182); (2) "HH2", Botrytis cinerea alpha pheromone (WCGRPGQPC, SEQ ID NO: 2183); (3) "HH3", Saccharomyces cerevisiae alpha pheromone (WHWLQLKPGQPMY, SEQ ID NO: 2184); (4) "HH31", rearranged Saccharomyces cerevisiae alpha pheromone (WHWLQLKPGQPMY, SEQ ID NO: 2185); cerevisiae alpha pheromone sequence (WKMGQYHQLPPLW, SEQ ID NO: 2185), (5) "HH35" Saccharomyces cerevisiae alpha pheromone with a C-terminal glycine (WHWLQLKPGQPMYG, SEQ ID NO: 2186); (6) "HH36" Saccharomyces cerevisiae alpha pheromone with an N-terminal glycine (GWHWLQLKPGQPMY, SEQ ID NO: 2187);(7) Saccharomyces cerevisiae alpha pheromone homodimer without the "HH37" linker (WHWLQLKPGQPMYWHWLQLKPGQPMY, SEQ ID NO: 2188); (8) Saccharomyces cerevisiae alpha pheromone homodimer with the "HH38" glycine linker (WHWLQLKPGQPMYGGGGSWHWLQLKPGQPMY, SEQ ID NO: 2189); (9) Saccharomyces cerevisiae alpha pheromone homodimer without the "HH4" linker and Fusarium graminearum (10) the heterodimer of Fusarium graminearum alpha pheromone and Saccharomyces cerevisiae alpha pheromone without the "HH42" linker, WCTWKGQPCWWHWLQLKPGQPMY (SEQ ID NO: 2233);

[0223] CGI factor peptides were prepared in 30% potato dextrose broth and filtered through a 1 mL syringe filter (PALL Acrodisc syringe filter with 0.2 micron Ultipor nylon membrane) since some precipitation was observed, therefore the CGI factor peptide concentrations presented in the table are treated as nominal (and minimum) concentrations. Results from this assay are provided in Table 10, with SESA values ​​normalized to untreated controls.

[0224] [Table 104]

[0225] Normalized values ​​against Fusarium proliferatum tested at a nominal concentration of 375 micromolar for the HH3, HH31, HH35, and HH36 peptides were significantly lower than the untreated control, and HH3, HH35, and HH36 also showed statistically significant antifungal activity at a nominal concentration of 250 micromolar. Four of the synthetic CGI factor peptides (HH37, HH38, HH4, and HH42) showed statistically significant antifungal activity at the lowest concentration tested, a nominal concentration of 100 micromolar, and notably, these peptides are homodimers or heterodimers that are longer than the naturally occurring alpha pheromone peptides tested and contain or do not contain additional linked amino acids, indicating that antifungal activity may be improved by selecting longer CGI peptides or by increasing the length of the CGI peptide sequence.

[0226] The foregoing disclosure describes aspects and embodiments of the present invention in some detail by way of illustration and example, but the descriptions and illustrations should not be construed as limiting the scope of the invention. Further embodiments are disclosed within the claims. The disclosures of all patent and scientific literature cited in this disclosure are expressly incorporated herein by reference in their entirety.

Claims

Claim 1 An antifungal composition for reducing the growth or reproduction of fungi, comprising: An effective amount of at least one conidium germination inhibitory (CGI) factor, CGI factor precursor, CGI factor fragment, or CGI factor motif, wherein The CGI factor comprises an amino acid sequence having at least 90% sequence identity with a sequence selected from the group consisting of SEQ ID NO: 2189, SEQ ID NO: 2240, SEQ ID NO: 961-1920, SEQ ID NO: 1957-2189, SEQ ID NO: 2194-2210, SEQ ID NO: 2215-2243, SEQ ID NO: 2457-3361, and SEQ ID NO: 5707-5731, or the CGI factor motif comprises at least one of SEQ ID NO: 1921-1956, The nucleotide sequence encoding the at least one CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is a CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif that does not exist in the genome of the fungus, Optionally, an agriculturally or pharmaceutically acceptable carrier, and an antifungal composition. Claim 2 The at least one CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif is provided as a polypeptide further comprising one or more of the group consisting of (a) a secretion signal peptide, (b) a localization signal, (c) a detectable or immunogenic marker, (d) a cleavage sequence, (e) an adjacent or linking amino acid sequence, (f) a cell-penetrating peptide, and (g) a self-assembling peptide. The antifungal composition according to claim 1. Claim 3 (a) One or more additional components selected from herbicides, insecticides, nematicides, fungicides (other than CGI factors, CGI factor precursors, CGI factor fragments, or CGI factor motifs), attractants, or baits, and / or (b) The antifungal composition according to claim 1 or claim 2, further comprising at least one agriculturally acceptable carrier selected from the group consisting of adjuvants, inert ingredients, dispersants, surfactants, tackifiers, binders, and stabilizers. Claim 4 The antifungal composition according to claim 1, formulated as a microparticle, solid, liquid, gel, liquid nanoparticle, suspension, emulsion, encapsulant, powder, granule, coating, film, coating, spray, seed coat, seed treatment, foliage spray treatment, foliage dip treatment, ready-to-use (RTU) formulation, produce coating, bait, suspension concentrate, tank mix, aerosol, root dip, soil drench, spray, soil treatment, irrigation formulation, or sprinkler formulation.

5. A method of reducing the growth or reproduction of a fungus, comprising providing the antifungal composition according to any one of claims 1 to 4 to the fungus, whereby the growth or reproduction of the fungus is reduced compared to a control fungus not provided with the antifungal composition.

6. The method according to claim 5, wherein the reduction in the growth or reproduction of the fungus comprises a reduction in the conidial germination or viability of the fungus.

7. The method according to claim 5, wherein the composition is provided to the fungus by contacting the fungus directly with the composition, or by delivering the composition to the environment of the fungus, or by expressing in the environment of the fungus a recombinant DNA construct comprising a nucleotide sequence encoding the at least one conidial CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif.

8. The method according to claim 5, wherein the fungus is a plant or animal pathogen, or a structural element of a fungal pathogen, and the method results in the prevention or reduction of a disease or damage caused by the fungus.

9. The method according to claim 5, wherein the fungus is at least one selected from the group consisting of Botrytis sp., Fusarium sp., Phytophthora sp., Zymoseptoria sp., Aspergillus sp., Magnaporthe sp., Puccinia sp., Blumeria sp., Mycosphaerella sp., Colletotrichum sp., Ustilago sp., Melampsora sp., Phakopsora sp., Rhizoctonia sp., Aspergillus sp., Candida sp., Coccidioides sp., Histoplasma sp., Cryptococcus sp., Pneumocystis sp., and Blastomyces sp.

10. The method according to claim 5, wherein the fungus is at least one selected from the group consisting of Botrytis sp., Fusarium sp., Phytophthora sp., and Zymoseptoria sp., and the CGI factor is provided as a polypeptide containing a multimer of fungal alpha pheromone or as a polypeptide containing a fungal alpha pheromone and a cell-permeable peptide.

11. The fungus is (a) Botrytis sp. or Fusarium sp., and the CGI factor has the amino acid sequence of SEQ ID NO: 2189, (b) Fusarium sp., Phytophthora sp., and Zymoseptoria sp., wherein the CGI factor has the amino acid sequence of SEQ ID NO: 2240, or (c) Cryptococcus sp., wherein the CGI factor has the amino acid sequence of SEQ ID NO: 2183, SEQ ID NO: 2184, or SEQ ID NO: 2189, the method according to claim 5.

12. A method for preventing or reducing a disease caused by a fungal pathogen of a plant, comprising providing the antifungal composition according to any one of claims 1 to 4 to the plant, whereby the disease caused by the fungal pathogen is prevented or reduced in the plant as compared to a control plant not provided with the antifungal composition.

13. The method according to claim 12, wherein the fungal pathogen is one or more selected from the group consisting of Botrytis sp., Fusarium sp., Phytophthora sp., Zymoseptoria sp., Aspergillus sp., Magnaporthe sp., Puccinia sp., Blumeria sp., Mycosphaerella sp., Colletotrichum sp., Ustilago sp., Melampsora sp., Phakopsora sp., and Rhizoctonia sp.

14. The method according to claim 12, wherein the fungal pathogen is at least one selected from the group consisting of Botrytis sp., Fusarium sp., Phytophthora sp., and Zymoseptoria sp., and the CGI factor is provided as a polypeptide comprising a multimer of a fungal alpha pheromone or as a polypeptide comprising a fungal alpha pheromone and a cell-permeable peptide.

15. The fungus is a) Botrytis sp. or Fusarium sp., and the CGI factor has the amino acid sequence of SEQ ID NO: 2189, b) Fusarium sp., Phytophthora sp., and Zymoseptoria sp., and the CGI factor has the amino acid sequence of SEQ ID NO: 2240, or c) Cryptococcus sp., and the CGI factor has the amino acid sequence of SEQ ID NO: 2183, SEQ ID NO: 2184, or SEQ ID NO: 2189, the method according to claim 12.

16. A method of treating a subject other than a human having a disease caused by a fungus or a subject other than a human at risk of having a disease caused by a fungus, comprising administering to the subject an antifungal composition according to any one of claims 1 to 4, whereby the fungal disease is prevented or reduced in the subject as compared to a control subject not provided with the antifungal composition.

17. The method according to claim 16, wherein the subject is an animal selected from the group consisting of invertebrates, amphibians, reptiles, birds, cartilaginous fish or bony fish, and non-human mammals.

18. A recombinant DNA construct comprising a heterologous promoter operably linked to a nucleic acid molecule comprising a nucleotide sequence encoding a conidium germination inhibition (CGI) factor, a CGI factor precursor, or a CGI factor fragment, wherein the nucleotide sequence is at least one CGI factor, at least one CGI factor precursor, or at least one CGI factor fragment encoding an amino acid sequence having at least 90% sequence identity with at least one of SEQ ID NO: 2189, SEQ ID NO: 2240, SEQ ID NO: 961 to 1920, SEQ ID NO: 1957 to 2189, SEQ ID NO: 2194 to 2210, SEQ ID NO: 2215 to 2243, SEQ ID NO: 2457 to 3361, or SEQ ID NO: 5707 to 5731, or encoding at least one CGI factor motif comprising at least one of SEQ ID NO: 1921 to 1956, a recombinant DNA construct, wherein said nucleotide sequence optionally has codons optimized for heterologous expression.

19. The recombinant DNA construct according to claim 18, wherein the nucleotide sequence encoding at least one CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif encodes (a) at least one copy of a CGI factor, (b) at least one copy of each of two or more CGI factors, (c) at least one CGI factor precursor, (d) at least one CGI factor fragment, (e) at least one CGI factor motif, or (f) any combination of (a) to (e).

20. The recombinant DNA construct according to claim 18, wherein the nucleotide sequence encoding at least one CGI factor, CGI factor precursor, CGI factor fragment, or CGI factor motif encodes a polypeptide further comprising one or more of the group consisting of (a) a secretion signal peptide, (b) a localization signal, (c) a detectable or immunogenic marker, (d) a cleavage sequence, (e) an adjacent or linked amino acid sequence, (f) a cell permeable peptide, and (g) a self-assembling peptide.

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