Engineered GPP synthases

Abstract

Geranyl pyrophosphate (GPP) is rapidly converted to farnesyl pyrophosphate in cells, which prevents the accumulation of GPP. Increased amounts of GPP production are desired for a variety of commercial purposes. This disclosure provides methods and compositions for increasing the production of geranyl pyrophosphate in cells. This disclosure provides methods and compositions related to expression of heterologous geranyl pyrophosphate synthases as well as chimeric geranyl pyrophosphate synthases.

Description

ENGINEERED GPP SYNTHASESCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority to U.S. Provisional Application Serial No. 63 / 587,312, filed October 2, 2023, the content of which is hereby incorporated by reference in its entirety.SEQUENCE LISTING

[0002] The instant application contains a Sequence Listing which has been submitted electronically in XML format and is hereby incorporated by reference in its entirety. Said XML copy, created on September 19, 2024, is named ISN-11625_SL.xml and is 39,489 bytes in size.FIELD OF THE INVENTION

[0003] The field of this invention is protein engineering and the production of geranyl pyrophosphate (GPP) in cells.BACKGROUND OF THE INVENTION

[0004] ERG20 / YJL167W (SEQ ID NOs: 6 and 18) is a Saccharomyces cerevisiae famesyl pyrophosphate (FPP) synthetase that catalyzes the formation of FPP units for downstream isoprenoid and sterol biosynthesis. ERG20 produces GPP as an intermediate while producing FPP. However, the conversion of GPP to FPP is so rapid that very low amounts of GPP are able to accumulate in wildtype 5. cerevisiae.

[0005] A modified ERG20 synthase has been produced to improve the GPP specificity of the enzyme. The modified ERG20 synthase contains two point mutations (F96W andN127W) and is referred to as ERG20WW (SEQ ID NOs: 7 and 19). See, for example, Ignea et al., ACS Synth. Biol., 3(5):298-306 (2014) and Zhao et al., Microbial Cell Factories, 16:Article 17, pp. 1-11 (2017). ERG20WW produces the highest GPP flux known in the art and allows for improved production of compounds that are dependent upon GPP as a substrate.

[0006] There remains a need in the art for an improvement over ERG20WW for an even higherGPP flux.SEQUENCES

[0007] Sequences used in this Specification are provided in Table 1.Table 1. Sequences used in this SpecificationSUMMARY OF THE INVENTION

[0008] In some aspects, this disclosure provides a polypeptide comprising an amino acid sequence at least 80% identical or similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, this disclosure provides a nucleic acid molecule comprising a polynucleotide sequence that encodes an amino acid sequence at least 80% identical or similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5.

[0009] In some aspects, this disclosure provides a cell comprising a heterologous polypeptide, or a nucleic acid molecule encoding the heterologous polypeptide, where the heterologous polypeptide comprises an amino acid sequence at least 80% identical or similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5 or 8 to 12.

[0010] In some aspects, this disclosure provides a chimeric protein, where the chimeric protein comprises a first portion comprising at least 10 amino acid residues that are identical to an amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7 and a second portion comprising at least 10 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12, where the chimeric protein produces a higher GPPto FPP ratio than at least one of SEQ ID NOs: 6 to 12 when the chimeric protein is active in a cell.

[0011] In some aspects, this disclosure provides a method of generating geranyl pyrophosphate (GPP) or a GPP-derivative in a cell, the method comprising: (a) providing a recombinant DNA construct to the cell, where the recombinant DNA construct comprises a promoter operably linked to a nucleic acid molecule encoding a heterologous polypeptide at least 80% identical or similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5 or 8 to 12; and (b) providing appropriate growth conditions for the cell, thereby allowing the cell to generate the GPP or GPP-derivative.

[0012] In some aspects, this disclosure provides a method of generating geranyl pyrophosphate (GPP) or a GPP-derivative in a cell, the method comprising: (a) providing a recombinant DNA construct to the cell, where the recombinant DNA construct comprises a promoter operably linked to a nucleic acid molecule encoding a chimeric protein, where the chimeric protein comprises a first portion comprising at least 10 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7 and a second portion comprising at least 10 amino acid residues that are identical to the amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12; and (b) providing appropriate growth conditions for the cell, thereby allowing the cell to generate the GPP or GPP-derivative.

[0013] In some aspects, this disclosure provides a method of modifying a cell, the method comprising: (a) providing to the cell: (i) a nucleic acid-guided nuclease, or a polynucleotide encoding the nucleic acid-guided nuclease; and (ii) at least one guide nucleic acid molecule, or a polynucleotide encoding the at least one guide nucleic acid molecule, where the at least one guide nucleic acid molecule is at least 80% identical or complementary to a gene encoding a geranyl pyrophosphate (GPP) synthase; and (b) providing the cell with conditions that allow the nucleic acid-guided nuclease and the at least one guide nucleic acid molecule to edit the gene encoding the GPP synthase to create a modified cell comprising a modified GPP synthase.BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Fig. 1 depicts the GPP synthase activity of different yeast strains expressing heterologous ERG20 homologs. The upper panel depicts mg / L geraniol and the lower panel depicts optical density. STR1200 expresses SEQ ID NO: 6; STR1205 expresses SEQ ID NO: 7; STR1406 expresses SEQ ID NO: 8; STR1407 expresses SEQ ID NO: 9; STR1408 expressesSEQ ID NO: 10; STR1506 expresses SEQ ID NO: 11; and STR1507 expresses SEQ ID NO: 12.

[0015] Fig. 2 depicts the GPP synthase activity of different yeast strains expressing either SEQ ID NO: 6 (STR1200), SEQ ID NO: 7 (STR1342), or SEQ ID NO: 1 (STR1633). GPP synthase activity is depicted by measuring geraniol.

[0016] Fig. 3 depicts the GPP synthase activity of different yeast strains expressing SEQ ID NO: 7 (STR1342), SEQ ID NO: 2 (STR2301), SEQ ID NO: 3 (STR2302), SEQ ID NO: 4 (STR2318), or SEQ ID NO: 5 (STR2320). GPP synthase activity is depicted by measuring geraniol.DETAILED DESCRIPTION

[0017] The description set forth below in connection with the appended drawings is intended to be a description of various, illustrative embodiments of the disclosed subj ect matter. Specific features and functionalities are described in connection with each illustrative embodiment; however, it will be apparent to those skilled in the art that the disclosed embodiments may be practiced without each of those specific features and functionalities. Moreover, all of the functionalities described in connection with one embodiment are intended to be applicable to the additional embodiments described herein except where expressly stated or where the feature or function is incompatible with the additional embodiments. For example, where a given feature or function is expressly described in connection with one embodiment but not expressly mentioned in connection with an alternative embodiment, it should be understood that the feature or function may be deployed, utilized, or implemented in connection with the alternative embodiment unless the feature or function is incompatible with the alternative embodiment.

[0018] The practice of the techniques described herein may employ, unless otherwise indicated, conventional techniques and descriptions of organic chemistry, polymer technology, molecular biology (including recombinant techniques), cell biology, biochemistry and sequencing technology, which are within the skill of those who practice in the art. Such conventional techniques include polymer array synthesis and hybridization and ligation of polynucleotides. Specific illustrations of suitable techniques can be had by reference to the examples herein. However, other equivalent conventional procedures can, of course, also be used. Such conventional techniques and descriptions can be found in standard laboratory manuals such as Green, et al., Eds. (1999), Genome Analysis: A Laboratory Manual Series(Vols. I-IV); Weiner, Gabriel, Stephens, Eds. (2007), Genetic Variation: A Laboratory Manual,' Dieffenbach, Dveksler, Eds. (2003), PCR Primer: A Laboratory Manual,' Mount (2004), Bioinformatics: Sequence and Genome Analysis,' Sambrook and Russell (2006), Condensed Protocols from Molecular Cloning: A Laboratory Manual,' and Sambrook and Russell (2002), Molecular Cloning: A Laboratory Manual (all from Cold Spring Harbor Laboratory Press); Stryer, L. (1995) Biochemistry (4th Ed.) W.H. Freeman, New York N.Y.; Gait, “Oligonucleotide Synthesis: A Practical Approach” 1984, IRL Press, London; Nelson and Cox (2000), Lehninger, Principles of Biochemistry 3rdEd., W. H. Freeman Pub., New York, N.Y.; Viral Vectors (Kaplift & Loewy, eds., Academic Press 1995); all of which are herein incorporated in their entirety by reference for all purposes. For mammalian / stem cell culture and methods see, e.g., Basic Cell Culture Protocols, Fourth Ed. (Helgason & Miller, eds., Humana Press 2005); Culture of Animal Cells, Seventh Ed. (Freshney, ed., Humana Press 2016); Microfluidic Cell Culture, Second Ed. (Borenstein, Vandon, Tao & Charest, eds., Elsevier Press 2018); Human Cell Culture (Hughes, ed., Humana Press 2011); 3D Cell Culture (Koledova, ed., Humana Press 2017); Cell and Tissue Culture: Laboratory Procedures in Biotechnology (Doyle & Griffiths, eds., John Wiley & Sons 1998); Essential Stem Cell Methods, (Lanza & Klimanskaya, eds., Academic Press 2011); Stem Cell Therapies: Opportunities for Ensuring the Quality and Safety of Clinical Offerings: Summary of a Joint Workshop (Board on Health Sciences Policy, National Academies Press 2014); Essentials of Stem Cell Biology, Third Ed., (Lanza & Atala, eds., Academic Press 2013); and Handbook of Stem Cells, (Atala & Lanza, eds., Academic Press 2012). CRISPR-specific techniques can be found in, e.g., Genome Editing and Engineering from TALENs and CRISPRs to Molecular Surgery, Appasani and Church (2018); and CRISPR: Methods and Protocols, Lindgren and Charpentier (2015); both of which are herein incorporated in their entirety by reference for all purposes.

[0019] Note that as used herein and in the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “an oligonucleotide” refers to one or more oligonucleotides. Furthermore, terms such as "first," "second," "third," etc., merely identify one of a number of portions, components, steps, operations, functions, and / or points of reference as disclosed herein, and likewise do not necessarily limit embodiments of the present disclosure to any particular configuration or orientation.

[0020] When the term “about” is used in reference to a number, it is understood to mean plus or minus 10%. For example, “about 100” would include from 90 to 110.

[0021] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. All publications mentioned herein are incorporated by reference for the purpose of describing and disclosing devices, methods and cell populations that may be used in connection with the presently described invention.

[0022] Where a range of values is provided, it is understood that each intervening value, between the upper and lower limit of that range and any other stated or intervening value in that stated range is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges, and are also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention.

[0023] When a grouping of alternatives is presented, any and all combinations of the members that make up that grouping of alternatives is specifically envisioned. For example, if an item is selected from a group consisting of A, B, C, and D, the inventors specifically envision each alternative individually (e.g., A alone, B alone, etc.), as well as combinations such as A, B, and D; A and C; B and C; etc. The term “and / or” when used in a list of two or more items means any one of the listed items by itself or in combination with any one or more of the other listed items. For example, the expression “A and / or B” is intended to mean either or both of A and B - i.e., A alone, B alone, or A and B in combination. The expression “A, B and / or C” is intended to mean A alone, B alone, C alone, A and B in combination, A and C in combination, B and C in combination, or A, B, and C in combination.

[0024] In the following description, numerous specific details are set forth to provide a more thorough understanding of the present invention. However, it will be apparent to one of ordinary skill in the art that the present invention may be practiced without one or more of these specific details. In other instances, well-known features and procedures well known to those skilled in the art have not been described in order to avoid obscuring the invention.

[0025] Any nucleic acid sequence or amino acid sequence provided herein is specifically envisioned for use in any cell provided herein.

[0026] ERG20 / YJL167W (SEQ ID NOs: 6 and 18) is a Saccharomyces cerevisiae famesyl pyrophosphate (FPP) synthetase that catalyzes the formation of FPP units for downstream isoprenoid and sterol biosynthesis. ERG20 produces GPP as an intermediate while producing FPP. However, the conversion of GPP to FPP is so rapid that very low amounts of GPP are able to accumulate in wildtype 5. cerevisiae.

[0027] GPP flux is difficult to directly quantify, so additional synthases are often integrated into cells which preferentially use either GPP or FPP and produce compounds that allow for a quantification of GPP flux and / or FPP flux. A geraniol synthase can be co-expressed with a modified GPP synthase. Without being limiting, geraniol synthases produce geraniol from GPP, and the geraniol can be quantified to determine GPP flux. See, for example, Simkin et al., Phytochemistry, 85:36-43 (January 2013). Similarly, a famesene synthase can be coexpressed with a modified GPP synthase. Without being limiting, famesene synthases produce famesene, and the famesene can be quantified to determine FPP flux.

[0028] In some aspects, a cell comprises a geraniol synthase or a nucleic acid sequence that encodes a geraniol synthase. In some aspects, a cell comprises a famesene synthase or a nucleic acid sequence that encodes a famesene synthase. In some aspects, a cell comprises a geraniol synthase or a nucleic acid sequence that encodes a geraniol synthase and a famesene synthase or a nucleic acid sequence that encodes a famesene synthase.

[0029] Although ERG20WW produces higher GPP flux than ERG20, an even higher GPP flux is desirable in the art. As is described below, Applicant has provided multiple solutions to this problem.

[0030] Prior to this disclosure, a modified version of ERG20, ERG20WW (SEQ ID NOs: 7 and 19), produced the highest known GPP flux in yeast. Here, Applicant provides multiple GPP synthases that outperform ERG20WW in regards to GPP flux.

[0031] In some aspects, a polypeptide comprises an amino acid sequence at least 70% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a polypeptide comprises an amino acid sequence at least 75% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a polypeptide comprises an amino acid sequence at least 80% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a polypeptide comprises an amino acid sequence at least 85% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a polypeptide comprises an amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a polypeptide comprises an amino acid sequence at least 91% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a polypeptide comprises an amino acid sequence at least 92% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a polypeptide comprises an amino acid sequence at least 93% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5.In some aspects, a polypeptide comprises an amino acid sequence at least 94% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a polypeptide comprises an amino acid sequence at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a polypeptide comprises an amino acid sequence at least 96% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a polypeptide comprises an amino acid sequence at least 97% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a polypeptide comprises an amino acid sequence at least 98% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a polypeptide comprises an amino acid sequence at least 99% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a polypeptide comprises an amino acid sequence 100% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5.

[0032] As used herein, the term “polypeptide” refers to a chain of at least two covalently linked amino acids. Polypeptides can be encoded by polynucleotides provided herein. Proteins provided herein can be encoded by nucleic acid molecules provided herein. Proteins can comprise polypeptides provided herein. As used herein, a “protein” refers to a chain of amino acid residues that is capable of providing structure or enzymatic activity to a cell.

[0033] The terms “percent identity” or “percent identical” as used herein in reference to two or more nucleotide or amino acid sequences is calculated by (i) comparing two optimally aligned sequences (nucleotide or amino acid) over a window of comparison (the “alignable” region or regions), (ii) determining the number of positions at which the identical nucleic acid base (for nucleotide sequences) or amino acid residue (for proteins and polypeptides) occurs in both sequences to yield the number of matched positions, (iii) dividing the number of matched positions by the total number of positions in the window of comparison, and then (iv) multiplying this quotient by 100% to yield the percent identity. If the “percent identity” is being calculated in relation to a reference sequence without a particular comparison window being specified, then the percent identity is determined by dividing the number of matched positions over the region of alignment by the total length of the reference sequence. Accordingly, for purposes of the present application, when two sequences (query and subject) are optimally aligned (with allowance for gaps in their alignment), the “percent identity” for the query sequence is equal to the number of identical positions between the two sequences divided bythe total number of positions in the query sequence over its length (or a comparison window), which is then multiplied by 100%.

[0034] For optimal alignment of sequences to calculate their percent identity, various pair-wise or multiple sequence alignment algorithms and programs are known in the art, such as ClustalW or Basic Local Alignment Search Tool® (BLAST™), etc., that can be used to compare the sequence identity or similarity between two or more nucleotide or amino acid sequences. Although other alignment and comparison methods are known in the art, the alignment and percent identity between two sequences (including the percent identity ranges described above) can be as determined by the ClustalW algorithm, see, e.g, Chenna et al., “Multiple sequence alignment with the Clustal series of programs,” Nucleic Acids Research 31: 3497-3500 (2003); Thompson et al., “Clustal W: Improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice,” Nucleic Acids Research 22: 4673-4680 (1994); Larkin MA et al., “Clustal W and Clustal X version 2.0,” Bioinformatics 23: 2947-48 (2007); and Altschul etal. "Basic local alignment search tool." J. Mol. Biol. 215:403-410 (1990), the entire contents and disclosures of which are incorporated herein by reference.

[0035] When percentage of sequence identity is used in reference to amino acids it is recognized that residue positions which are not identical often differ by conservative amino acid substitutions, where amino acid residues are substituted for other amino acid residues with similar chemical properties (e.g., charge or hydrophobicity) and therefore do not change the functional properties of the molecule. When sequences differ in conservative substitutions, the percent sequence identity can be adjusted upwards to correct for the conservative nature of the substitution. Sequences that differ by such conservative substitutions are said to have “sequence similarity” or “similarity.”

[0036] Without being limiting, two aliphatic (e.g., glycine, alanine, valine, leucine, isoleucine) amino acid residues can be substituted for each other in a conservative substitution; two hydroxyl (e.g., serine, cysteine, threonine, methionine) amino acid residues can be substituted for each other in a conservative substitution; two aromatic (e.g., phenylalanine, tyrosine, tryptophan) amino acid residues can be substituted for each other in a conservative substitution; two basic (e.g., histidine, lysine, arginine) amino acid residues can be substituted for each other in a conservative substitution; and two acid (e.g, aspartate, glutamate, asparagine, glutamine) amino acid residues can be substituted for each other in a conservative substitution.

[0037] In some aspects, a polypeptide comprises an amino acid sequence at least 70% similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In someaspects, a polypeptide comprises an amino acid sequence at least 75% similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a polypeptide comprises an amino acid sequence at least 80% similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a polypeptide comprises an amino acid sequence at least 85% similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a polypeptide comprises an amino acid sequence at least 90% similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a polypeptide comprises an amino acid sequence at least 91% similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a polypeptide comprises an amino acid sequence at least 92% similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a polypeptide comprises an amino acid sequence at least 93% similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a polypeptide comprises an amino acid sequence at least 94% similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a polypeptide comprises an amino acid sequence at least 95% similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a polypeptide comprises an amino acid sequence at least 96% similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a polypeptide comprises an amino acid sequence at least 97% similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a polypeptide comprises an amino acid sequence at least 98% similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a polypeptide comprises an amino acid sequence at least 99% similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a polypeptide comprises an amino acid sequence 100% similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5.

[0038] In some aspects, this disclosure provides a nucleic acid molecule comprising a polynucleotide encoding any polypeptide provided herein.

[0039] The use of the term “polynucleotide” or “nucleic acid molecule” is not intended to limit the present disclosure to polynucleotides comprising deoxyribonucleic acid (DNA). For example, ribonucleic acid (RNA) molecules encoded by the DNA molecules provided herein are also envisioned. Those of ordinary skill in the art will recognize that polynucleotides and nucleic acid molecules can comprise ribonucleotides and combinations of ribonucleotides and deoxy ribonucleotides. Such deoxyribonucleotides and ribonucleotides include both naturallyoccurring molecules and synthetic analogues. The polynucleotides of the present disclosure also encompass all forms of sequences including, but not limited to, single-stranded forms, double-stranded forms, hairpins, stem-and-loop structures, and the like. In some aspects, a nucleic acid molecule provided herein is a DNA molecule. In some aspects, a nucleic acid molecule is an RNA molecule. In some aspects, a nucleic acid molecule is single-stranded. In some aspects, a nucleic acid molecule is double-stranded. In some aspects, a nucleic acid molecule encodes a polypeptide.

[0040] In some aspects, a nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide having an amino acid sequence at least 70% identical to a sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide having an amino acid sequence at least 75% identical to a sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide having an amino acid sequence at least 80% identical to a sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide having an amino acid sequence at least 85% identical to a sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide having an amino acid sequence at least 90% identical to a sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide having an amino acid sequence at least 91% identical to a sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide having an amino acid sequence at least 92% identical to a sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide having an amino acid sequence at least 93% identical to a sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide having an amino acid sequence at least 94% identical to a sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide having an amino acid sequence at least 95% identical to a sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide having an amino acid sequence at least 96% identical to a sequence selected from the groupconsisting of SEQ ID NOs: 1 to 5. In some aspects, a nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide having an amino acid sequence at least 97% identical to a sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide having an amino acid sequence at least 98% identical to a sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide having an amino acid sequence at least 99% identical to a sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide having an amino acid sequence 100% identical to a sequence selected from the group consisting of SEQ ID NOs: 1 to 5.

[0041] In some aspects, a nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide having an amino acid sequence at least 70% similar to a sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, anucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide having an amino acid sequence at least 75% similar to a sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide having an amino acid sequence at least 80% similar to a sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide having an amino acid sequence at least 85% similar to a sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide having an amino acid sequence at least 90% similar to a sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide having an amino acid sequence at least 91% similar to a sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide having an amino acid sequence at least 92% similar to a sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide having an amino acid sequence at least 93% similar to a sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide having an amino acid sequence at least 94% similar to a sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a nucleic acid molecule comprises apolynucleotide sequence encoding a polypeptide having an amino acid sequence at least 95% similar to a sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide having an amino acid sequence at least 96% similar to a sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide having an amino acid sequence at least 97% similar to a sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide having an amino acid sequence at least 98% similar to a sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide having an amino acid sequence at least 99% similar to a sequence selected from the group consisting of SEQ ID NOs: 1 to 5. In some aspects, a nucleic acid molecule comprises a polynucleotide sequence encoding a polypeptide having an amino acid sequence 100% similar to a sequence selected from the group consisting of SEQ ID NOs: 1 to 5.

[0042] In some aspects, a polynucleotide sequence comprises a nucleic acid sequence 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% identical to SEQ ID NO: 13. In some aspects, a polynucleotide sequence comprises a nucleic acid sequence 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% identical to SEQ ID NO: 14. In some aspects, a polynucleotide sequence comprises anucleic acid sequence 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% identical to SEQ ID NO: 15. In some aspects, a polynucleotide sequence comprises a nucleic acid sequence 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% identical to SEQ ID NO: 16. In some aspects, a polynucleotide sequence comprises a nucleic acid sequence 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% identical to SEQ ID NO: 17. In some aspects, a polynucleotide sequence comprises a nucleic acid sequence 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% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 13 to 17.

[0043] In some aspects, this disclosure provides a chimeric protein, where the chimeric protein comprises a first portion comprising at least 10 amino acid residues that are identical to an amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7 and a second portion comprising at least 10 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, the first portion is positioned on the amino-terminus side of the second portion. In some aspects, the first portion is positioned on the carboxy -terminus side of the second portion. In some aspects, a chimeric protein further comprises a third portion, where the third portion comprises at least 10 amino acid residues. In some aspects, a chimeric protein produces a higher GPP to FPP ratio than at least one of SEQ ID NOs: 6 to 12 when the chimeric protein is active in a cell. In some aspects, a chimeric protein produces a higher GPP derivative to FPP derivative ratio than at least one of SEQ ID NOs: 6 to 12 when the chimeric protein is active in a cell. In some aspects, a chimeric protein produces a higher GPP plus GPP derivative to FPP plus FPP derivative ratio than at least one of SEQ ID NOs: 6 to 12 when the chimeric protein is active in a cell.

[0044] As used herein, a “chimeric protein” refers to a protein that comprises an amino acid sequence that joins the amino acid sequence of two or more different donor proteins. Each donor protein contributes a “portion” of its sequence to a chimeric protein. It will be understood that a “portion” refers to any contiguous segment of a donor protein between 10 amino acids and the full length of the donor protein. It will also be understood that a single protein could provide multiple portions to a chimeric protein. As a non-limiting example, a chimeric protein can comprise amino acid residues 1 to 15 of Protein A, followed by amino acid residues 1 to 20 of Protein B, followed by amino acid residues 60 to 80 of Protein A. In some aspects, a protein provides the same portion to a chimeric protein more than once. As a non-limiting example, chimeric protein can comprise amino acid residues 1 to 15 of Protein A, followed by amino acid residues 1 to 20 of Protein B, followed by amino acid residues 1 to 15 of Protein A. In some aspects, a donor protein comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 6 to 12.

[0045] As used herein, a chimeric protein is “active” when the chimeric protein is capable of performing an enzymatic function (e.g, producing GPP from precursor molecule(s)).

[0046] In some aspects, a third portion of a chimeric protein comprises at least 10 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 12 amino acid residuesthat are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 15 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 20 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 25 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 30 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 35 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 40 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 45 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 50 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 55 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 60 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 65 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 70 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 75 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 80 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 85 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 90 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 95 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 100 amino acid residuesthat are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 125 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 150 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 175 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 200 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 250 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 275 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 280 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 290 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 300 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 310 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 320 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 330 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises at least 340 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7.

[0047] In some aspects, a second portion of a chimeric protein comprises between 10 amino acid residues and 340 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a second portion of a chimeric protein comprises between 10 amino acid residues and 330 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a second portion of a chimeric protein comprises between 10 amino acid residues and 320 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a second portion of a chimeric protein comprises between 10 amino acid residues and 310 aminoacid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a second portion of a chimeric protein comprises between 10 amino acid residues and 300 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a second portion of a chimeric protein comprises between 10 amino acid residues and 290 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a second portion of a chimeric protein comprises between 10 amino acid residues and 280 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a second portion of a chimeric protein comprises between 10 amino acid residues and 250 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a second portion of a chimeric protein comprises between 10 amino acid residues and 200 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a second portion of a chimeric protein comprises between 10 amino acid residues and 150 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises between 10 amino acid residues and 325 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises between 10 amino acid residues and 300 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises between 10 amino acid residues and 250 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises between 10 amino acid residues and 200 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises between 10 amino acid residues and 150 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises between 10 amino acid residues and 100 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises between 10 amino acid residues and 75 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises between 10 amino acid residues and 50 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises between 10 amino acid residues and 40 amino acid residues that are identical to the amino acidsequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises between 10 amino acid residues and 30 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some aspects, a third portion of a chimeric protein comprises between 10 amino acid residues and 20 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7.

[0048] In some aspects, a second portion of a chimeric protein comprises at least 10 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises at least 12 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises at least 15 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises at least 20 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises at least 25 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises at least 30 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises at least 35 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises at least 40 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises at least 45 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises at least 50 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises at least 55 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises at least 60 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises at least 65 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises at least 70amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises at least 75 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises at least 80 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises at least 85 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises at least 90 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises at least 95 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises at least 100 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises at least 125 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises at least 150 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises at least 175 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises at least 200 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises at least 250 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises at least 275 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises at least 280 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises at least 300 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 11. In some aspects, a second portion of a chimeric protein comprises at least 325 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 10. In someaspects, a second portion of a chimeric protein comprises at least 350 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 and 9. In some aspects, a second portion of a chimeric protein comprises at least 400 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 and 9. In some aspects, a second portion of a chimeric protein comprises at least 450 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 8. In some aspects, a second portion of a chimeric protein comprises at least 475 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 8. In some aspects, a second portion of a chimeric protein comprises at least 500 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 8.

[0049] In some aspects, a second portion of a chimeric protein comprises between 10 amino acid residues and 500 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 8. In some aspects, a second portion of a chimeric protein comprises between 10 amino acid residues and 450 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 8. In some aspects, a second portion of a chimeric protein comprises between 10 amino acid residues and 400 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 8. In some aspects, a second portion of a chimeric protein comprises between 10 amino acid residues and 400 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 and 9. In some aspects, a second portion of a chimeric protein comprises between 10 amino acid residues and 375 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 and 9. In some aspects, a second portion of a chimeric protein comprises between 10 amino acid residues and 350 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 and 9. In some aspects, a second portion of a chimeric protein comprises between 10 amino acid residues and 325 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 10. In some aspects, a second portion of a chimeric protein comprises between 10 amino acid residues and 300 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 11. In some aspects, a second portion of a chimeric protein comprises between 10 amino acid residues and 280 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises between 10 amino acid residues and 250 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimericprotein comprises between 10 amino acid residues and 200 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises between 10 amino acid residues and 150 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises between 10 amino acid residues and 100 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises between 10 amino acid residues and 75 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises between 10 amino acid residues and 50 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises between 10 amino acid residues and 40 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises between 10 amino acid residues and 30 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12. In some aspects, a second portion of a chimeric protein comprises between 10 amino acid residues and 20 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12.

[0050] In some aspects, a third portion of a chimeric protein comprises at least 10 amino acid residues. In some aspects, a third portion of a chimeric protein comprises at least 12 amino acid residues. In some aspects, a third portion of a chimeric protein comprises at least 15 amino acid residues. In some aspects, a third portion of a chimeric protein comprises at least 20 amino acid residues. In some aspects, a third portion of a chimeric protein comprises at least 25 amino acid residues. In some aspects, a third portion of a chimeric protein comprises at least 30 amino acid residues. In some aspects, a third portion of a chimeric protein comprises at least 35 amino acid residues. In some aspects, a third portion of a chimeric protein comprises at least 40 amino acid residues. In some aspects, a third portion of a chimeric protein comprises at least 45 amino acid residues. In some aspects, a third portion of a chimeric protein comprises at least 50 amino acid residues. In some aspects, a third portion of a chimeric protein comprises at least 55 amino acid residues. In some aspects, a third portion of a chimeric protein comprises at least 60 amino acid residues. In some aspects, a third portion of a chimeric protein comprises at least 65 amino acid residues. In some aspects, a third portion of a chimeric protein comprises at least 70 amino acidresidues. In some aspects, a third portion of a chimeric protein comprises at least 75 amino acid residues. In some aspects, a third portion of a chimeric protein comprises at least 80 amino acid residues. In some aspects, a third portion of a chimeric protein comprises at least 85 amino acid residues. In some aspects, a third portion of a chimeric protein comprises at least 90 amino acid residues. In some aspects, a third portion of a chimeric protein comprises at least 95 amino acid residues. In some aspects, a third portion of a chimeric protein comprises at least 100 amino acid residues. In some aspects, a third portion of a chimeric protein comprises at least 125 amino acid residues. In some aspects, a third portion of a chimeric protein comprises at least 150 amino acid residues. In some aspects, a third portion of a chimeric protein comprises at least 175 amino acid residues. In some aspects, a third portion of a chimeric protein comprises at least 200 amino acid residues. In some aspects, a third portion of a chimeric protein comprises at least 250 amino acid residues. In some aspects, a third portion of a chimeric protein comprises at least 300 amino acid residues. In some aspects, a third portion of a chimeric protein comprises at least 325 amino acid residues. In some aspects, a third portion of a chimeric protein comprises at least 350 amino acid residues. In some aspects, a third portion of a chimeric protein comprises at least 400 amino acid residues. In some aspects, a third portion of a chimeric protein comprises at least 450 amino acid residues. In some aspects, a third portion of a chimeric protein comprises at least 500 amino acid residues.

[0051] In some aspects, a third portion of a chimeric protein comprises between 10 amino acid residues and 500 amino acid residues. In some aspects, a third portion of a chimeric protein comprises between 10 amino acid residues and 400 amino acid residues. In some aspects, a third portion of a chimeric protein comprises between 10 amino acid residues and 300 amino acid residues. In some aspects, a third portion of a chimeric protein comprises between 10 amino acid residues and 200 amino acid residues. In some aspects, a third portion of a chimeric protein comprises between 10 amino acid residues and 100 amino acid residues. In some aspects, a third portion of a chimeric protein comprises between 10 amino acid residues and 75 amino acid residues. In some aspects, a third portion of a chimeric protein comprises between 10 amino acid residues and 50 amino acid residues. In some aspects, a third portion of a chimeric protein comprises between 10 amino acid residues and 40 amino acid residues. In some aspects, a third portion of a chimeric protein comprises between 10 amino acid residues and 30 amino acid residues. In some aspects, a third portion of a chimeric protein comprises between 10 amino acid residues and 20 amino acid residues.

[0052] In some aspects, a third portion of a chimeric protein is positioned at the aminoterminus of the chimeric protein. In some aspects, a third portion of a chimeric protein ispositioned at the carboxy-terminus of a chimeric protein. In some aspects, a third portion of a chimeric protein is positioned between a third portion and a second portion of the chimeric protein. In some aspects, a third portion of a chimeric protein is positioned on the aminoterminus side of a third portion of the chimeric protein. In some aspects, a third portion of a chimeric protein is positioned on the amino-terminus side of a second portion of the chimeric protein. In some aspects, a third portion of a chimeric protein is positioned on the carboxyterminus side of a third portion of the chimeric protein. In some aspects, a third portion of a chimeric protein is positioned on the carboxy -terminus side of a second portion of the chimeric protein.

[0053] In some aspects, two portions (e.g, a third portion and a second portion; a second portion and a first portion; a first portion and a third portion) of a chimeric protein are contiguous, with no intervening or linking amino acid residues between the two portions. In some aspects, two portions (e.g, a third portion and a second portion; a second portion and a first portion; a first portion and a third portion) of a chimeric protein are separated by a linker comprising at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 20, at least 25, at least 30, at least 35, at least 40, at least 45, at least 50, at least 60, at least 70, at least 80, at least 90, or at least 100 amino acid residues.

[0054] In some aspects, this disclosure provides a nucleic acid molecule encoding any chimeric protein provided herein.

[0055] In some aspects, a polynucleotide sequence is operably linked to a promoter. As commonly understood in the art, the term “promoter” refers to a DNA sequence that contains an RNA polymerase binding site, a transcription start site, and / or a TATA box and assists or promotes the transcription and expression of an associated transcribable polynucleotide sequence and / or gene (or transgene). A promoter can be synthetically produced, varied, or derived from a known or naturally occurring promoter sequence or other promoter sequence. A promoter can also include a chimeric promoter comprising a combination of two or more heterologous sequences. A promoter of the present application can thus include variants of promoter sequences that are similar in composition, but not identical to, other promoter sequence(s) known or provided herein.

[0056] In some aspects, a nucleic acid molecule encoding a heterologous polypeptide is operably linked to a promoter. In some aspects, a promoter is a constitutive promoter. As used herein, a “constitutive” promoter refers to a promoter that is active in vivo at all times. Typically, the activity of a constitutive promoter is limited only by the presence of a suitableRNA polymerase at a suitable concentration. Non-limiting examples of constitutive promoters include: a glyceraldehyde-3-phosphate dehydrogenase (TDH3) promoter, a triose phosphate isomerase (TPI1) promoter, an enolase 2 (EN02) promoter, an alcohol dehydrogenase (ADH1) promoter, and a translational elongation factor EFl -a promoter. In some aspects, a constitutive promoter is selected from the group consisting of a gly ceraldehy de-3-phosphate dehydrogenase (TDH3) promoter, a triose phosphate isomerase (TPI1) promoter, an enolase 2 (EN02) promoter, an alcohol dehydrogenase (ADH1) promoter, and a translational elongation factor EFl -a promoter.

[0057] In some aspects, a promoter is an inducible promoter. As used herein, an “inducible promoter” refers to a regulated promoter that becomes active (e.g., it drives the expression of an operably linked sequence) in a cell in response to a specific stimulus.

[0058] In some aspects, an inducible promoter is a temperature-inducible promoter. As used herein, a “temperature inducible promoter” refers to a promoter that becomes active above or below a threshold temperature.

[0059] In some aspects, a promoter is a chemically-inducible promoter. As used herein, a “chemically inducible promoter” refers to a promoter that becomes active in the presence of a specific chemical. Typically, chemically inducible promoters are inactive if the inducing chemical is not present or if the inducing chemical is not present at a high enough concentration to activate the promoter. In some aspects, a chemically inducible promoter is selected from the group consisting of a tetracycline ON promoter, an alcohol-inducible promoter, and a steroid- inducible promoter. In some aspects, a chemically inducible promoter is a rhamnose-inducible promoter. As used herein, a “rhamnose-inducible promoter” refers to a promoter that is active in the presence of rhamnose. As used herein, an “alcohol-inducible promoter” refers to a promoter that is active in the presence of an alcohol. As used herein, a “steroid-inducible promoter” refers to a promoter that is active in the presence of a steroid. In some aspects, a chemically inducible promoter is a lac promoter. In some aspects, a chemically inducible promoter is selected from the group consisting of a rhamnose-inducible promoter and a lac promoter.

[0060] As used herein, “operably linked” refers to a functional linkage between two or more elements. For example, an operable linkage between a polynucleotide of interest and a regulatory sequence (e.g., a promoter) is a functional link that allows for expression of the polynucleotide of interest. Operably linked elements may be contiguous or non-contiguous.

[0061] In some aspects, a promoter is a heterologous promoter. As used herein, “heterologous” refers to a nucleic acid sequence or amino acid sequence that originates from a foreign species,or, if from the same species, is substantially modified from its native form in composition and / or genomic locus by deliberate human intervention.

[0062] In some aspects, a polynucleotide comprises a heterologous promoter operably linked to a nucleic acid sequence encoding an amino acid sequence 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% identical to SEQ ID NO:6. In some aspects, a polynucleotide comprises a heterologous promoter operably linked to a nucleic acid sequence encoding an amino acid sequence 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% identical to SEQ ID NO:7. In some aspects, a polynucleotide comprises a heterologous promoter operably linked to a nucleic acid sequence encoding an amino acid sequence 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% identical to SEQ ID NO:8. In some aspects, a polynucleotide comprises a heterologous promoter operably linked to a nucleic acid sequence encoding an amino acid sequence 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% identical to SEQ ID NO:9. In some aspects, a polynucleotide comprises a heterologous promoter operably linked to a nucleic acid sequence encoding an amino acid sequence 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% identical to SEQ ID NO:10. In some aspects, a polynucleotide comprises a heterologous promoter operably linked to a nucleic acid sequence encoding an amino acid sequence 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% identical to SEQ ID NO:11. In some aspects, a polynucleotide comprises a heterologous promoter operably linked to a nucleic acid sequence encoding an amino acid sequence 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% identical to SEQ ID NO:12.

[0063] In some aspects, a polynucleotide comprises a heterologous promoter operably linked to a nucleic acid sequence 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% identical to SEQ ID NO: 18. In some aspects, a polynucleotide comprises a heterologous promoter operably linked to a nucleic acid sequence 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% identical to SEQ ID NO: 19. In some aspects, a polynucleotide comprises a heterologous promoter operably linked to a nucleic acid sequence 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% identical to SEQ ID NO: 20. In some aspects, a polynucleotide comprises a heterologous promoter operably linked to a nucleic acid sequence 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% identical to SEQ ID NO: 21. In some aspects, a polynucleotide comprises a heterologous promoter operably linked to a nucleic acid sequence 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% identical to SEQ ID NO: 22. In some aspects, a polynucleotide comprises a heterologous promoter operably linked to a nucleic acid sequence 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% identical to SEQ ID NO: 23. In some aspects, a polynucleotide comprises a heterologous promoter operably linked to a nucleic acid sequence 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% identical to SEQ ID NO: 24.

[0064] In some aspects, a polynucleotide molecule comprises an enhancer element. An “enhancer element” refers to a region of DNA that can be bound by proteins to increase the likelihood that transcription of an operably linked sequence will occur. Without being limiting, an enhancer element typically comprises between 50 nucleotides and 1500 nucleotides. In some aspects, an enhancer element is positioned upstream (e.g, 5' to) a sequence that is to be transcribed. In some aspects, an enhancer element is positioned downstream (e.g, 3' to) a sequence that is to be transcribed. In some aspects, a nucleic acid molecule encoding a heterologous polypeptide is operably linked to an enhancer element.

[0065] In some aspects, a polynucleotide molecule comprises a transcription terminator. Any transcription terminator suitable for terminating transcription of a polynucleotide can be used.

[0066] Various species exhibit particular bias for certain codons of a particular amino acid. Codon bias (differences in codon usage between organisms) often correlates with the efficiency of translation of messenger RNA (mRNA), which is in turn believed to be dependent on, among other things, the properties of the codons being translated and the availability of particular transfer RNA (tRNA) molecules. The predominance of selected tRNAs in a cell is generally a reflection of the codons used most frequently in peptide synthesis. Accordingly, genes can be tailored for optimal gene expression in a given organism based on codon optimization. Codon usage tables are readily available, for example, at the "Codon Usage Database" available at www[dot]kazusa[dot]or[dot]jp[forward slash]codon and these tables can be adapted in a number of ways. See Nakamura et al., 2000, Nucl. Acids Res. 28:292. Computer algorithms for codon optimizing a particular sequence for expression in a particular host cell are also available, such as Gene Forge (Aptagen; Jacobus, PA), are also available.

[0067] In some aspects, a polynucleotide sequence is codon optimized for a particular organism.

[0068] As used herein, “codon optimization” refers to a process of modifying a nucleic acid sequence for enhanced expression in a host cell of interest by replacing at least one codon (e.g., at least 1, at least 2, at least 3, at least 4, at least 5, at least 10, at least 15, at least 20, at least 25, at least 50, or more than 51 codons) of a sequence with codons that are more frequently or most frequently used in the genes of the host cell while maintaining the original amino acid sequence (e.g., introducing silent mutations). In some aspects, an entire coding sequence in a polynucleotide is codon optimized for a particular organism or host cell.

[0069] In some aspects, a polynucleotide sequence is codon optimized for a eukaryotic cell. In some aspects, a polynucleotide sequence is codon optimized for a prokaryotic cell. In some aspects, a polynucleotide sequence is codon optimized for a fungal cell. In some aspects, a polynucleotide sequence is codon optimized for a plant cell. In some aspects, a polynucleotide sequence is codon optimized for an animal cell.

[0070] In some aspects, a nucleic acid molecule is provided within a vector. As used herein, a “vector” refers to a circular, double-stranded DNA molecule that is physically separate from chromosomal DNA. In some aspects, a vector is capable of replication in vivo. In some aspects, a vector comprises a recombinant DNA construct.

[0071] As used herein, a “recombinant DNA construct” refers to a DNA molecule or sequence that is man-made and not normally found in nature and / or is present in a context which it is not normally found in nature. In some aspects, a recombinant DNA construct comprises a combination of two or more polynucleotide sequences that do not naturally occur together inthe same manner without human intervention. In some aspects, a nucleic acid molecule comprises a recombinant DNA construct.

[0072] In some aspects, a cell comprises any polypeptide provided herein. In some aspects, a cell comprises any polynucleotide sequence provided herein. In some aspects, a cell comprises any nucleic acid molecule provided herein.

[0073] In some aspects, a cell comprises a heterologous polypeptide, or a nucleic acid molecule encoding the heterologous polypeptide, where the heterologous polypeptide comprises an amino acid sequence at least 75% identical or similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5 or 8 to 12. In some aspects, a cell comprises a heterologous polypeptide, or a nucleic acid molecule encoding the heterologous polypeptide, where the heterologous polypeptide comprises an amino acid sequence at least 80% identical or similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5 or 8 to 12. In some aspects, a cell comprises a heterologous polypeptide, or a nucleic acid molecule encoding the heterologous polypeptide, where the heterologous polypeptide comprises an amino acid sequence at least 85% identical or similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5 or 8 to 12. In some aspects, a cell comprises a heterologous polypeptide, or a nucleic acid molecule encoding the heterologous polypeptide, where the heterologous polypeptide comprises an amino acid sequence at least 90% identical or similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5 or 8 to 12. In some aspects, a cell comprises a heterologous polypeptide, or a nucleic acid molecule encoding the heterologous polypeptide, where the heterologous polypeptide comprises an amino acid sequence at least 91% identical or similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5 or 8 to 12. In some aspects, a cell comprises a heterologous polypeptide, or a nucleic acid molecule encoding the heterologous polypeptide, where the heterologous polypeptide comprises an amino acid sequence at least 92% identical or similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5 or 8 to 12. In some aspects, a cell comprises a heterologous polypeptide, or a nucleic acid molecule encoding the heterologous polypeptide, where the heterologous polypeptide comprises an amino acid sequence at least 93% identical or similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5 or 8 to 12. In some aspects, a cell comprises a heterologous polypeptide, or a nucleic acid molecule encoding the heterologous polypeptide, where the heterologous polypeptide comprises an amino acid sequence at least 94% identical or similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5 or 8 to 12. In some aspects, a cell comprises aheterologous polypeptide, or a nucleic acid molecule encoding the heterologous polypeptide, where the heterologous polypeptide comprises an amino acid sequence at least 95% identical or similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5 or 8 to 12. In some aspects, a cell comprises a heterologous polypeptide, or a nucleic acid molecule encoding the heterologous polypeptide, where the heterologous polypeptide comprises an amino acid sequence at least 96% identical or similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5 or 8 to 12. In some aspects, a cell comprises a heterologous polypeptide, or a nucleic acid molecule encoding the heterologous polypeptide, where the heterologous polypeptide comprises an amino acid sequence at least 97% identical or similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5 or 8 to 12. In some aspects, a cell comprises a heterologous polypeptide, or a nucleic acid molecule encoding the heterologous polypeptide, where the heterologous polypeptide comprises an amino acid sequence at least 98% identical or similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5 or 8 to 12. In some aspects, a cell comprises a heterologous polypeptide, or a nucleic acid molecule encoding the heterologous polypeptide, where the heterologous polypeptide comprises an amino acid sequence at least 99% identical or similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5 or 8 to 12. In some aspects, a cell comprises a heterologous polypeptide, or a nucleic acid molecule encoding the heterologous polypeptide, where the heterologous polypeptide comprises an amino acid sequence 100% identical or similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5 or 8 to 12.

[0074] In some aspects, a cell is a prokaryotic cell. In some aspects a prokaryotic cell is an Escherichia cell. In some aspects, a prokaryotic cell is a Bacillus cell. In some aspects, a prokaryotic cell is a Pseudomonas cell. In some aspects, a prokaryotic cell is a Corynebacterium cell.

[0075] In some aspects, a cell is a eukaryotic cell. In some aspects, a cell is a fungal cell. In some aspects, a cell is a plant cell. In some aspects, a cell is an animal cell. In some aspects, an animal cell is an in vitro or ex vivo culture. In some aspects, an animal cell is a non-human animal cell.

[0076] In some aspects, a cell is ayeast cell. In some aspects, ayeast cell is a Saccharomycotina cell. In some aspects, a cell is a Schizosaccharomycetes cell. In some aspects, a yeast cell is a Saccharomycetales cell.

[0077] In some aspects, a yeast cell is an Arxula cell. In some aspects, a yeast cell is an Aureobasidium cell. In some aspects, a yeast cell is a Brettanomyces cell. In some aspects, ayeast cell is a Candida cell. In some aspects, a yeast cell is a Cryotpococcus cell. In some aspects, a yeast cell is aDekkera cell. In some aspects, a yeast cell is an Eremothecium cell. In some aspects, a yeast cell is a Geotrichum cell. In some aspects, a yeast cell is a Kluyveromyces cell. In some aspects, a yeast cell is a Komagataella cell. In some aspects, a yeast cell is a Lachancea cell. In some aspects, a yeast cell is a Leucosporidium cell. In some aspects, a yeast cell is aMeyerozyma cell. In some aspects, a yeast cell is an Ogataea cell. In some aspects, a yeast cell is aRhodotorula cell. In some aspects, a yeast cell is a Saccharomyces cell. In some aspects, a yeast cell is a Scheffersomyces cell. In some aspects, a yeast cell is a Schizosaccharomyces cell. In some aspects, a yeast cell is aSporidiobolus cell. In some aspects, a yeast cell is a Torula cell. In some aspects, a yeast cell is a Torulaspora cell. In some aspects, a yeast cell is a Trichosporon cell. In some aspects, a yeast cell is a Wickerhamomyces cell. In some aspects, a yeast cell is a Yarrowia cell. In some aspects, a yeast cell is a Zygosaccharomyces cell.

[0078] In some aspects, a yeast cell is an Arxula adeninivorans cell. In some aspects, a yeast cell is an Aureobasidium melanogenum cell. In some aspects, a yeast cell is a Brettanomyces bruxellensis cell. In some aspects, a yeast cell is a Candida albicans cell. In some aspects, a yeast cell is a Candida antarctica cell. In some aspects, a yeast cell is a Candida auris cell. In some aspects, a yeast cell is a Candida blankii cell. In some aspects, a yeast cell is a Candida dubliniensis cell. In some aspects, a yeast cell is a Candida glabrata cell. In some aspects, a yeast cell is a Candida humilis cell. In some aspects, a yeast cell is a Candida krusei cell. In some aspects, a yeast cell is a Candida lusitaniae cell. In some aspects, a yeast cell is a Candida oleophila cell. In some aspects, a yeast cell is a Candida parapsilosis cell. In some aspects, a yeast cell is a Candida stellata cell. In some aspects, a yeast cell is a Candida telluris cell. In some aspects, a yeast cell is a Candida tropicalis cell. In some aspects, a yeast cell is a Candida viswanathii cell. In some aspects, a yeast cell is a Cryotpococcus gattii cell. In some aspects, a yeast cell is a Cryotpococcus neoformans cell. In some aspects, a yeast cell is a Dekkera anomala cell. In some aspects, a yeast cell is an Eremothecium gossypii cell. In some aspects, a yeast cell is a Geotrichum candidum cell. In some aspects, a yeast cell is a Kluyveromyces lactis cell. In some aspects, a yeast cell is a Kluyveromyces marxianus cell. In some aspects, a yeast cell is a Komagataella pastoris cell. In some aspects, a yeast cell is a Lachancea kluyveri cell. In some aspects, a yeast cell is a Leucosporidium frigidum cell. In some aspects, a yeast cell is aMeyerozyma guiliermondii cell. In some aspects, a yeast cell is an Ogataea polymorpha cell. In some aspects, a yeast cell is aRhodotorula glutinis cell. In some aspects, a yeast cell is aRhodotorula mucilaginosa cell. In some aspects, a yeast cell is aRhodotorula rubra cell. Insome aspects, a yeast cell is a Saccharomyces bayanus cell. In some aspects, a yeast cell is a Saccharomyces boulardii cell. In some aspects, a yeast cell is a Saccharomyces cerevisiae cell. In some aspects, a yeast cell is a Saccharomyces exiguus cell. In some aspects, a yeast cell is a Saccharomyces florentinus cell. In some aspects, a yeast cell is a Saccharomyces pastorianus cell. In some aspects, a yeast cell is a Saccharomyces telluris cell. In some aspects, a yeast cell is a Saccharomyces uvarum cell. In some aspects, a yeast cell is a Scheffer somyces stipitis cell. In some aspects, a yeast cell is a Schizosaccharomyces pombe cell. In some aspects, a yeast cell is a Sporidiobolus salmonicolor cell. In some aspects, a yeast cell is a Torulaspora delbrueckii cell. In some aspects, a yeast cell is a Torulaspora globosa cell. In some aspects, a yeast cell is a Trichosporon asteroides cell. In some aspects, a yeast cell is a Trichosporon mycotoxinovorans cell. In some aspects, a yeast cell is a Wickerhamomyces anomalus cell. In some aspects, a yeast cell is a Yarrowia lipolytica cell. In some aspects, a yeast cell is a Zygosaccharomyces bailii cell. In some aspects, a yeast cell is a Zygosaccharomyces bayanus cell.

[0079] As used herein, a “control cell” refers to a cell that is essentially identical genetically to a modified cell except for the modification(s) present in the modified cell and provides a reference point for measuring changes in the genotype or phenotype of a modified cell. As a non-limiting example, if a modified cell comprises a heterologous polypeptide and / or a nucleic acid molecule encoding the heterologous polypeptide encoding a GPP provided herein, the control cell would lack the heterologous polypeptide and nucleic acid molecule encoding the heterologous polypeptide. A control cell should be of the same species and the same type or strain as the modified cell.

[0080] As used herein, “comparable conditions” refers to similar environmental conditions, such that neither genotype nor environmental conditions would contribute to, or explain, any differences observed between a control cell and a modified cell other than the modification present in the modified cell. It is appreciated that comparable conditions does not require identical conditions.

[0081] “Appropriate growth conditions” for a cell refers to environmental growth conditions that allow a cell to survive and / or multiple or otherwise reproduce. Such conditions include, without being limiting, growth media, oxygen content, pH, humidity, and temperature. It will be appreciated that the conditions do not necessarily need to be the conditions required for optimal growth for the chosen species of cell. In some aspects, cells can be shaken, stirred, rocked, vortexed, or otherwise agitated. Suitable conditions for cellular growth of many species are known in the art. For example, see Son and Taylor, Curr. Protoc., l:e20 (2021) and / orElbing and Brent, Curr Protoc Mol Biol, 125:e83 (2019) for descriptions of suitable growth conditions for E. coli,' Salari and Salari, Electron Physician, 9(l):3592-3597 (2017) for a description of suitable growth conditions for Saccharomyces cerevisiae.’ and Petersen andRussell, Cold Spring Harb Protoc, 2016(3):pdb.top079764 for a description of suitable growth conditions for Schizosaccharomyces pombe.

[0082] In some aspects, cells are incubated or grown at a temperature of about 20°C. In some aspects, cells are incubated or grown at a temperature of about 21°C. In some aspects, cells are incubated or grown at a temperature of about 22°C. In some aspects, cells are incubated or grown at a temperature of about 23°C. In some aspects, cells are incubated or grown at a temperature of about 24°C. In some aspects, cells are incubated or grown at a temperature of about 25°C. In some aspects, cells are incubated or grown at a temperature of about 28°C. In some aspects, cells are incubated or grown at a temperature of about 30°C. In some aspects, cells are incubated or grown at a temperature of about 32°C. In some aspects, cells are incubated or grown at a temperature of about 34°C. In some aspects, cells are incubated or grown at a temperature of about 37°C. In some aspects, cells are incubated or grown at a temperature of about 40°C. In some aspects, cells are incubated or grown at a temperature of about 42°C. In some aspects, cells are incubated or grown at a temperature of about 45°C.

[0083] In some aspects, cells are incubated or grown at a temperature of between 15°C and 45°C. In some aspects, cells are incubated or grown at a temperature of between 20°C and 45°C. In some aspects, cells are incubated or grown at a temperature of between 25°C and 45°C. In some aspects, cells are incubated or grown at a temperature of between 30°C and 40°C.

[0084] In some aspects, cells are incubated c >r grown at a temperature of at least 10°C. In some aspects, cells are incubated or grown at a temperature of at least 15°C. In some aspects, cells are incubated or grown at a temperature of at least 20°C. In some aspects, cells are incubated or grown at a temperature of at least 25°C. In some aspects, cells are incubated or grown at a temperature of at least 30°C. In some aspects, cells are incubated or grown at a temperature of at least 35°C. In some aspects, cells are incubated or grown at a temperature of at least 37°C.

[0085] In some aspects, cells are grown or incubated at a pH of about 5. In some aspects, cells are grown or incubated at a pH of about 5.5. In some aspects, cells are grown or incubated at a pH of about 6. In some aspects, cells are grown or incubated at a pH of about 6.5. In some aspects, cells are grown or incubated at a pH of about 7. In some aspects, cells are grown or incubated at a pH of about 7.5. In some aspects, cells are grown or incubated at a pH of about 8. In some aspects, cells are grown or incubated at a pH of about 8.5. In some aspects, cells aregrown or incubated at a pH of about 9. In some aspects, cells are grown or incubated at a pH of between 5 and 9. In some aspects, cells are grown or incubated at a pH of at least 6. In some aspects, cells are grown or incubated at a pH of at least 7. In some aspects, cells are grown or incubated at a pH of at least 8.

[0086] In some aspects, cells can be grown in a liquid medium. Any liquid medium suitable for growth of a chosen cell can be used. In some aspects, cells are grown in Luria-Bertani (LB) liquid broth. In some aspects, cells are grown in YPD liquid broth.

[0087] In some aspects, cells can be grown on a solid medium. Any solid medium suitable for growth of a chosen cell can be used. In some aspects, cells are grown on LB agar plates. In some aspects, cells are grown on or in a medium comprising peptone. In some aspects, cells are grown on or in a medium comprising yeast extract. In some aspects, cells are grown on or in a medium comprising dextrose. In some aspects, cells are grown on or in a medium comprising glucose. In some aspects, cells are grown on or in a medium comprising an antibiotic. In some aspects, cells are grown on or in a medium comprising agar. In some aspects, cells are grown on or in a medium comprising water.

[0088] In some aspects, cells can be grown in an aerobic environment. In some aspects, cells are grown in an anaerobic environment.

[0089] In some aspects, a solid medium comprises an antibiotic. In some aspects, a liquid medium comprises an antibiotic.

[0090] In some aspects, a cell provided herein produces an increased ratio of geranyl pyrophosphate (GPP) to famesyl pyrophosphate (FPP) as compared to a control cell grown under comparable conditions.

[0091] Without being limiting, one method to measure GPP in a cell is to include a reporter gene such as geraniol synthase in the cell of interest. Geraniol synthase produces geraniol from GPP. Then, a measurement of geraniol can serve as a proxy to measure GPP. Geraniol synthase is categorized by the Enzyme Commission as EC 3.1.7.11.

[0092] Also without being limiting, one method to measure FPP in a cell is to include a reporter gene such as famesene synthase in the cell of interest. Famesene synthase produces famesene from FPP. A measurement of famesene can serve as a proxy to measure FPP. Famesene synthase is categorized by the Enzyme Commission as EC 4.2.3.47.

[0093] In some aspects, a cell provided herein produces an increased ratio of GPP derivative to FPP derivative as compared to a control cell grown under comparable conditions. As used herein, a “GPP derivative” refers to any compound derived from GPP. Non-limiting examples of GPP derivatives include geraniol, limonene, / Epinene, a-pinene. / >-phellandrene. sabinene,perillyl alcohol, linalool, a-terpineol, and nerol. In some aspects, a GPP derivative is selected from the group consisting of geraniol, limonene, / / -pinene. a- pinene, / / -phellandrene. sabinene, perillyl alcohol, linalool, a-terpineol, and nerol. In some aspects, a GPP derivative is geraniol. In some aspects, a GPP derivative is a monoterpenoid. See, for example, Liu et al., J Ind Microbiol Biotechnol, 48(9-10):kuab065 (2021). In some aspects, a measurement of a GPP derivative can serve as a proxy to measure GPP activity.

[0094] As used herein, an “FPP derivative” refers to any compound derived from FPP. Nonlimiting examples of FPP derivatives include famesene, collobial, punctaporonane, silphinane, presilphiperfolane, capnellane, africanane, tremulane, hirsutane, ceratopicane, cucumane, pleurotellane, sterpurane, iso-lactanane, A’ A’-germacradienyl. bisabolyl, bergamotane, cycloheptenyl, trichothecene, aristolochene, germacrene A, a-muurolene, daucene, trans- dauca-4(l l),8-diene, [3-barbatene, a-barbatene, longibomeol, a-acorenol, a-cuprenene, trichodiene, acoradiene, fusariumdiene, e / ti-zonarene, cadinene, (-)- germacrene D, cubebol, pentalenene, illudin, lactanane, bullerane, hydrogammane, and formannosane. In some aspects, an FPP deriviative is famesene. In some aspects, an FPP derivative is selected from the group consisting of famesene, collobial, punctaporonane, silphinane, presilphiperfolane, capnellane, africanane, tremulane, hirsutane, ceratopicane, cucumane, pleurotellane, sterpurane, iso- lactanane, / / .A’-germacradienyl. bisabolyl, bergamotane, cycloheptenyl, trichothecene, aristolochene, germacrene A, a-muurolene, daucene, tra«5-dauca-4(l l),8-diene, [3-barbatene, a-barbatene, longibomeol, a-acorenol, a-cuprenene, trichodiene, acoradiene, fusariumdiene, cyv-zonarene. cadinene, (-)- germacrene D, cubebol, pentalenene, illudin, lactanane, bullerane, hydrogammane, and formannosane. In some aspects, an FPP derivative is a sesquiterpenoid. See, for example, Dai et al., J Fungi (Basel), 7(12): 1026 (2021). In some aspects, a measurement of an FPP derivative can serve as a proxy to measure FPP activity.

[0095] In some aspects, a cell provided herein comprises a geraniol synthase reporter gene. In some aspects, a cell provided herein comprises a famesene synthase reporter gene. In some aspects, a cell provided herein comprises both a geraniol synthase reporter gene and a famesene synthase reporter gene. It will be appreciated that those in the art will be able to recognize and use additional reporter genes, if needed, if it is desirable to measure GPP derivatives and / or FPP derivatives in a cell.

[0096] In some aspects, a cell provided herein produces an increased ratio of GPP plus GPP derivatives to FPP plus FPP derivatives as compared to a control cell grown under comparable conditions. As used herein, “GPP plus GPP derivatives” refers to a summation of GPP and any GPP derivatives (e.g., without being limiting, geraniol). As used herein, “FPP plus FPPderivatives” refers to a summation of FPP and any FPP derivatives (e.g, without being limiting, famesene).

[0097] Without being limiting, if a cell produces the same amount of GPP and FPP, the ratio of GPP to FPP can be expressed as 1 : 1. If a cell produces twice as much GPP as FPP, the ratio of GPP to FPP can be expressed as 2: 1. Conversely, if a cell produces half as much GPP as FPP, the ratio of GPP to FPP can be expressed as either 0.5: 1 or 1 :2.

[0098] An increased ratio of GPP to FPP means that the cell produces more GPP and / or less FPP as compared to a control cell grown under comparable conditions.

[0099] In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of at least 0.1% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of at least 0.25% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of at least 0.5% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of at least 0.75% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of at least 1% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of at least 2.5% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of at least 5% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of at least 7.5% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of at least 10% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of at least 15% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of at least 20% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of at least 25% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of at least 30% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of at least 40% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of at least 50% as compared to a control cell grown under comparable conditions. In some aspects,an increased ratio of GPP to FPP comprises a GPP increase of at least 60% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of at least 70% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of at least 80% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of at least 90% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of at least 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of at least 150% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of at least 200% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of at least 250% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of at least 300% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of at least 400% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of at least 500% as compared to a control cell grown under comparable conditions.

[0100] In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between0.1% and 1000% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 0. 1% and 750% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 0.1% and 500% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 0.1% and 250% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 0.1% and 225% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 0.1% and 200% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 0.1% and 175% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 0.1% and 150% as compared to a control cell grown under comparable conditions. Insome aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 0.1% and 125% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 0.1% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 0.1% and 90% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 0.1% and 80% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 0.1% and 70% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 0.1% and 60% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 0.1% and 50% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 0.1% and 40% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 0.1% and 30% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 0.1% and 20% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 0.1% and 10% as compared to a control cell grown under comparable conditions.

[0101] In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 10% and 750% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 10% and 500% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 10% and 250% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 10% and 225% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 10% and 200% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 10% and 175% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 10% and 150% as compared to a control cell grown under comparable conditions. Insome aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 10% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 10% and 75% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 10% and 50% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 10% and 25% as compared to a control cell grown under comparable conditions.

[0102] In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 25% and 750% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 25% and 500% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 25% and 250% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 25% and 225% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 25% and 200% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 25% and 175% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 25% and 150% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 25% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 25% and 75% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises a GPP increase of between 25% and 50% as compared to a control cell grown under comparable conditions.

[0103] In some aspects, an increased ratio of GPP to FPP comprises an FPP decrease of at least 0.1% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises an FPP decrease of at least 0.5% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises an FPP decrease of at least 1% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises an FPP decrease of at least 5% as compared to a control cell grown under comparable conditions. Insome aspects, an increased ratio of GPP to FPP comprises an FPP decrease of at least 10% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises an FPP decrease of at least 20% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises an FPP decrease of at least 30% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises an FPP decrease of at least 40% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises an FPP decrease of at least 50% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises an FPP decrease of at least 60% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises an FPP decrease of at least 70% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises an FPP decrease of at least 80% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises an FPP decrease of at least 90% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises an FPP decrease of at least 99% as compared to a control cell grown under comparable conditions.

[0104] In some aspects, an increased ratio of GPP to FPP comprises an FPP decrease of between 0.1% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises an FPP decrease of between 0.1% and 75% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises an FPP decrease of between 0.1% and 50% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises an FPP decrease of between 0.1% and 25% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises an FPP decrease of between 0.5% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises an FPP decrease of between 1% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises an FPP decrease of between 5% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises an FPP decrease of between 10% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises an FPP decrease of between 25%and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises an FPP decrease of between 50% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises an FPP decrease of between 75% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises an FPP decrease of between 1% and 50% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises an FPP decrease of between 1% and 25% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP to FPP comprises an FPP decrease of between 25% and 75% as compared to a control cell grown under comparable conditions.

[0105] In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of at least 0.1% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of at least 0.25% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of at least 0.5% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of at least 0.75% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of at least 1% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of at least 2.5% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of at least 5% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of at least 7.5% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of at least 10% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of at least 15% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of at least 20% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of at least 25% as compared to a controlcell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of at least 30% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of at least 40% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of at least 50% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of at least 60% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of at least 70% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of at least 80% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of at least 90% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of at least 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of at least 150% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of at least 200% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of at least 250% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of at least 300% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of at least 400% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of at least 500% as compared to a control cell grown under comparable conditions.

[0106] In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 0.1% and 1000% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 0.1% and 750% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative toFPP derivative comprises a GPP derivative increase of between 0.1% and 500% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 0.1% and 250% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 0.1% and 225% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 0.1% and 200% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 0.1% and 175% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 0.1% and 150% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 0.1% and 125% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 0.1% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 0.1% and 90% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 0.1% and 80% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 0.1% and 70% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 0.1% and 60% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 0.1% and 50% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 0.1% and 40% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 0.1% and 30% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 0.1% and 20% as compared to a control cellgrown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 0.1% and 10% as compared to a control cell grown under comparable conditions.

[0107] In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 10% and 750% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 10% and 500% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 10% and 250% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 10% and 225% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 10% and 200% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 10% and 175% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 10% and 150% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 10% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 10% and 75% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 10% and 50% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 10% and 25% as compared to a control cell grown under comparable conditions.

[0108] In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 25% and 750% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 25% and 500% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 25% and 250% as comparedto a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 25% and 225% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 25% and 200% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 25% and 175% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 25% and 150% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 25% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 25% and 75% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of between 25% and 50% as compared to a control cell grown under comparable conditions.

[0109] In some aspects, an increased ratio of GPP derivative to FPP derivative comprises an FPP derivative decrease of at least 0.1% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises an FPP derivative decrease of at least 0.5% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises an FPP derivative decrease of at least 1% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises an FPP derivative decrease of at least 5% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises an FPP derivative decrease of at least 10% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises an FPP derivative decrease of at least 20% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises an FPP derivative decrease of at least 30% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises an FPP derivative decrease of at least 40% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises an FPP derivative decrease of at least 50% as compared to a control cell grown undercomparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises an FPP derivative decrease of at least 60% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises an FPP derivative decrease of at least 70% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises an FPP derivative decrease of at least 80% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises an FPP derivative decrease of at least 90% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises an FPP derivative decrease of at least 99% as compared to a control cell grown under comparable conditions.

[0110] In some aspects, an increased ratio of GPP derivative to FPP derivative comprises an FPP derivative decrease of between 0.1% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises an FPP derivative decrease of between 0.1% and 75% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises an FPP derivative decrease of between 0.1% and 50% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises an FPP derivative decrease of between 0.1% and 25% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises an FPP derivative decrease of between 0.5% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises an FPP derivative decrease of between 1% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises an FPP derivative decrease of between 5% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises an FPP derivative decrease of between 10% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises an FPP derivative decrease of between 25% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises an FPP derivative decrease of between 50% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises an FPPderivative decrease of between 75% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises an FPP derivative decrease of between 1% and 50% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises an FPP derivative decrease of between 1% and 25% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP derivative to FPP derivative comprises an FPP derivative decrease of between 25% and 75% as compared to a control cell grown under comparable conditions.

[0111] In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of at least 0.1% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of at least 0.25% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of at least 0.5% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of at least 0.75% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of at least 1% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of at least 2.5% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of at least 5% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of at least 7.5% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of at least 10% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of at least 15% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of at least 20% as compared to a control cellgrown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of at least 25% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of at least 30% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of at least 40% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of at least 50% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of at least 60% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of at least 70% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of at least 80% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of at least 90% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of at least 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of at least 150% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of at least 200% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of at least 250% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of at least 300% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of at least 400% as compared to a control cell grown under comparable conditions. In some aspects, an increasedratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of at least 500% as compared to a control cell grown under comparable conditions.

[0112] In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 0.1% and 1000% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 0.1% and 750% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 0.1% and 500% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 0.1% and 250% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 0.1% and 225% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 0.1% and 200% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 0.1% and 175% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 0.1% and 150% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 0.1% and 125% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 0.1% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 0.1% and 90% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 0.1% and 80% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPPplus FPP derivative comprises a GPP plus GPP derivative increase of between 0.1% and 70% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 0.1% and 60% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 0.1% and 50% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 0.1% and 40% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 0.1% and 30% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 0.1% and 20% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 0.1% and 10% as compared to a control cell grown under comparable conditions.

[0113] In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 10% and 750% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 10% and 500% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 10% and 250% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 10% and 225% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 10% and 200% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 10% and 175% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 10% and 150%as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 10% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 10% and 75% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 10% and 50% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 10% and 25% as compared to a control cell grown under comparable conditions.

[0114] In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 25% and 750% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 25% and 500% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 25% and 250% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 25% and 225% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 25% and 200% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 25% and 175% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 25% and 150% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 25% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 25% and 75% as compared to a control cell grown under comparable conditions. In some aspects, anincreased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a GPP plus GPP derivative increase of between 25% and 50% as compared to a control cell grown under comparable conditions.

[0115] In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises an FPP plus FPP derivative decrease of at least 0.1% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises an FPP plus FPP derivative decrease of at least 0.5% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises an FPP plus FPP derivative decrease of at least 1% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises an FPP plus FPP derivative decrease of at least 5% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises an FPP plus FPP derivative decrease of at least 10% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises an FPP plus FPP derivative decrease of at least 20% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises an FPP plus FPP derivative decrease of at least 30% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises an FPP plus FPP derivative decrease of at least 40% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises an FPP plus FPP derivative decrease of at least 50% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises an FPP plus FPP derivative decrease of at least 60% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises an FPP plus FPP derivative decrease of at least 70% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises an FPP plus FPP derivative decrease of at least 80% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises an FPP plus FPP derivative decrease of at least 90% as compared to a control cell grown undercomparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises an FPP plus FPP derivative decrease of at least 99% as compared to a control cell grown under comparable conditions.

[0116] In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises an FPP plus FPP derivative decrease of between 0.1% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises an FPP plus FPP derivative decrease of between 0.1% and 75% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises an FPP plus FPP derivative decrease of between 0.1% and 50% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises an FPP plus FPP derivative decrease of between 0.1% and 25% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises an FPP plus FPP derivative decrease of between 0.5% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises an FPP plus FPP derivative decrease of between 1% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises an FPP plus FPP derivative decrease of between 5% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises an FPP plus FPP derivative decrease of between 10% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises an FPP plus FPP derivative decrease of between 25% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises an FPP plus FPP derivative decrease of between 50% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises an FPP plus FPP derivative decrease of between 75% and 100% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises an FPP plus FPP derivative decrease of between 1% and 50% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPPplus FPP derivative comprises an FPP plus FPP derivative decrease of between 1% and 25% as compared to a control cell grown under comparable conditions. In some aspects, an increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises an FPP plus FPP derivative decrease of between 25% and 75% as compared to a control cell grown under comparable conditions.

[0117] In some aspects, this disclosure provides a method of generating GPP or a GPP- derivative in a cell, the method comprising: (a) providing a recombinant DNA construct to the cell, where the recombinant DNA construct comprises a promoter operably linked to a nucleic acid molecule encoding a heterologous polypeptide at least 80% identical or similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5 or 8 to 12; and (b) providing appropriate growth conditions for the cell, thereby allowing the cell to generate the GPP or the GPP-derivative.

[0118] In some aspects, this disclosure provides a method of generating GPP or a GPP- derivative in a cell, the method comprising: (a) providing a recombinant DNA construct to the cell, where the recombinant DNA construct comprises a promoter operably linked to a nucleic acid molecule encoding a chimeric protein; and (b) providing appropriate growth conditions for the cell, thereby allowing the cell to generate the GPP or the GPP-derivative. In some aspects, this disclosure provides a method of generating GPP or a GPP-derivative in a cell, the method comprising: (a) providing a recombinant DNA construct to the cell, where the recombinant DNA construct comprises a promoter operably linked to a nucleic acid molecule encoding a chimeric protein, where the chimeric protein comprises a first portion comprising at least 10 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7 and a second portion comprising at least 10 amino acid residues that are identical to the amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12; and (b) providing appropriate growth conditions for the cell, thereby allowing the cell to generate the GPP or the GPP-derivative.

[0119] Numerous methods for transforming (e.g., providing) cells with anucleic acid molecule or polypeptide are known in the art, which can be used according to methods of the present application. Any suitable method or technique for transformation of a cell known in the art can be used according to present methods. Non-limiting methods for transformation of cells includes polyethylene glycol-mediated transformation, biolistic transformation, liposome- mediated transfection, viral transduction, the use of one or more delivery particles, and electroporation. In some aspects, a method comprises introducing one or more nucleic acid molecules or polypeptides to a cell using a method selected from the group consisting ofpolyethylene glycol-mediated transformation, biolistic transformation, liposome-mediated transfection, viral transduction, the use of one or more delivery particles, and electroporation.

[0120] In some aspects, a method comprises providing a cell with a nucleic acid molecule via polyethylene glycol-mediated transformation. In some aspects, a method comprises providing a cell with a nucleic acid molecule via biolistic transformation. In some aspects, a method comprises providing a cell with a nucleic acid molecule via liposome-mediated transfection. In some aspects, a method comprises providing a cell with a nucleic acid molecule via viral transduction. In some aspects, a method comprises providing a cell with a nucleic acid molecule via use of one or more delivery particles. In some aspects, a method comprises providing a cell with a nucleic acid molecule via microinjection. In some aspects, a method comprises providing a cell with a nucleic acid molecule via electroporation. In some aspects, a method comprises providing a cell with a nucleoprotein complex via microinjection. In some aspects, a method comprises providing a cell with a nucleoprotein complex via electroporation.

[0121] Other methods for transformation, such as vacuum infiltration, pressure, sonication, and silicon carbide fiber agitation, are also known in the art and envisioned for use with any method provided herein.

[0122] Methods of transforming cells are well known by persons of ordinary skill in the art. For instance, transformation of yeast cells is described in Kawai et al., Bioengineered Bugs, 1(6): 395-403 (2010); Gietz and Schiestl, Nature Protocols, 2:31-34 (2007); and Gietz and Woods, BioTechniques, 30(4):816— 831 (2001). Specific instructions for transforming plant cells by microprojectile bombardment with particles coated with nucleic acid molecules (e.g., biolistic transformation) are found in U.S. Patent Nos. 5,550,318; 5,538,880 6,160,208; 6,399,861; and 6,153,812.

[0123] Lipofection is described in e.g., U.S. Pat. Nos. 5,049,386, 4,946,787; and 4,897,355) and lipofection reagents are sold commercially (e.g., Transfectam™ and Lipofectin™). Cationic and neutral lipids that are suitable for efficient receptor-recognition lipofection of polynucleotides include those of Feigner, WO 91 / 17424; WO 91 / 16024.

[0124] Delivery vehicles, vectors, particles, nanoparticles, formulations and components thereof for expression of one or more elements of a nucleic acid molecule are as used in WO 2014 / 093622. In some aspects, a method of providing a nucleic acid molecule or a protein to a cell comprises delivery via a delivery particle. In some aspects, a method of providing a nucleic acid molecule to a cell comprises delivery via a delivery vesicle. In some aspects, a delivery vesicle is selected from the group consisting of an exosome and a liposome. In some aspects, a method of providing a nucleic acid molecule to a cell comprises delivery via a viral vector.In some aspects, a viral vector is selected from the group consisting of an adenovirus vector, a lentivirus vector, and an adeno-associated viral vector. In another aspect, a method providing a nucleic acid molecule to a cell comprises delivery via a nanoparticle. In some aspects, a method providing a nucleic acid molecule to a cell comprises microinjection. In some aspects, a method providing a nucleic acid molecule to a cell comprises poly cations. In some aspects, a method providing a nucleic acid molecule to a cell comprises a cationic oligopeptide.

[0125] In some aspects, a delivery particle is selected from the group consisting of an exosome, an adenovirus vector, a lentivirus vector, an adeno-associated viral vector, a nanoparticle, a poly cation, and a cationic oligopeptide. In some aspects, a method provided herein comprises the use of one or more delivery particles. In another aspect, a method provided herein comprises the use of two or more delivery particles. In another aspect, a method provided herein comprises the use of three or more delivery particles.

[0126] Suitable agents to facilitate transfer of nucleic acid molecules into a cell include agents that increase permeability of the cell to oligonucleotides or polynucleotides. Such agents to facilitate transfer of the composition into a cell include a chemical agent, or a physical agent, or combinations thereof. Chemical agents for conditioning includes (a) surfactants, (b) organic solvents, aqueous solutions, or aqueous mixtures of organic solvents, (c) oxidizing agents, (e) acids, (I) bases, (g) oils, (h) enzymes, or combinations thereof.

[0127] Agents for laboratory conditioning of a cell to permeation by polynucleotides include, e.g., application of a chemical agent, enzymatic treatment, heating or chilling, treatment with positive or negative pressure, or ultrasound treatment.

[0128] In some aspects, this disclosure provides a method of modifying a cell, the method comprising (a) providing to the cell: (i) a nucleic acid-guided nuclease, or a polynucleotide encoding the nucleic-acid guided nuclease; and (ii) at least one guide nucleic acid molecule, or a polynucleotide encoding the at least one guide nucleic acid molecule, where the at least one guide nucleic acid molecule is at least 80% identical or complementary to a gene encoding a geranyl pyrophosphate (GPP) synthase; and (b) providing the cell with conditions that allow the nucleic acid-guided nuclease and the at least one guide nucleic acid molecule to form a complex and edit the gene encoding the GPP synthase to create a modified cell comprising a modified GPP synthase. In some aspects, step (a) further comprises providing the cell with (iii) at least one donor template, or a polynucleotide encoding the at least one donor template. In some aspects, the modified cell exhibits increased production of GPP as compared to a control cell that comprises an unmodified GPP synthase. In some aspects, the modified cell exhibitsincreased production of a GPP derivative as compared to a control cell that comprises an unmodified GPP synthase.

[0129] In some aspects, a donor template comprises any nucleic acid molecule provided herein. In some aspects, a donor template encodes any polypeptide provided herein. In some aspects, a donor template encodes any chimeric polypeptide provided herein. In some aspects, a donor template comprises between 20 nucleotides and 2000 nucleotides. In some aspects, a donor template comprises between 20 nucleotides and 1500 nucleotides. In some aspects, a donor template comprises between 20 nucleotides and 1000 nucleotides.

[0130] In some aspects, a nucleic acid-guided nuclease is, or is derived from, Cas9 or Casl2a (also known as Cpfl). Without being limiting, additional examples of nucleic-acid guided nucleases can be found in U.S. Patent No. 9,982,279; U.S. Patent No. 10,604,746; U.S. Patent No. 10,704,033; U.S. Patent No. 10,883,095; and U.S. Patent No. 11,306,298.

[0131] In some aspects, the at least one guide nucleic acid molecule is 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% identical or complementary to a gene encoding a GPP synthase.

[0132] Without being limiting, the following embodiments are specifically envisioned:1. A polypeptide comprising an amino acid sequence at least 80% identical or similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5.2. A nucleic acid molecule comprising a polynucleotide sequence encoding the polypeptide of embodiment 1.3. The nucleic acid molecule of embodiment 2, wherein the polynucleotide sequence is at least 80% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 13 to 17.4. The nucleic acid molecule of embodiment 2, wherein the polynucleotide sequence is operably linked to a promoter.5. The nucleic acid molecule of embodiment 4, wherein the promoter is a constitutive promoter.6. The nucleic acid molecule of embodiment 5, wherein the constitutive promoter is selected from the group consisting of a glyceraldehyde-3-phosphate dehydrogenase (TDH3) promoter, atriose phosphate isomerase (TPI1) promoter, an enolase 2 (ENO2) promoter, an alcohol dehydrogenase (ADH1) promoter, and a translational elongation factor EFl-a promoter. The nucleic acid molecule of embodiment 4, wherein the promoter is an inducible promoter. The nucleic acid molecule of embodiment 7, wherein the inducible promoter is selected from the group consisting of a temperature-inducible promoter and a chemically -inducible promoter.The nucleic acid molecule of any one of embodiments 2 to 8, wherein the polynucleotide sequence is operably linked to an enhancer element. The nucleic acid molecule of any one of embodiments 2 to 9, wherein the polynucleotide sequence is codon optimized for a fungal cell. The nucleic acid molecule of any one of embodiments 2 to 9, wherein the polynucleotide sequence is codon optimized for a prokaryotic cell. The nucleic acid molecule of any one of embodiments 2 to 9, wherein the polynucleotide sequence is codon optimized for a plant cell. The nucleic acid molecule of any one of embodiments 2 to 9, wherein the polynucleotide sequence is codon optimized for an animal cell. The nucleic acid molecule of any one of embodiments 2 to 13, wherein the nucleic acid molecule is within a vector. A cell comprising the polypeptide of embodiment 1 or the nucleic acid molecule of any one of embodiments 2 to 14. The cell of embodiment 15, wherein the cell is a yeast cell. The cell of embodiment 16, wherein the yeast cell is a Saccharomyces cerevisiae cell. The cell of embodiment 16, wherein the yeast cell is selected from the group consisting of an Arxula cell, anAureobasidium cell, aBrettanomyces cell, a Candida cell, a Cryotpococcus cell, a Dekkera cell, an Eremothecium cell, a Geotrichum cell, a Kluyveromyces cell, a Komagataella cell, a Lachancea cell, a Leucosporidium cell, aMeyerozyma cell, an Ogataea cell, aRhodotorula cell, a Saccharomyces cell, a Scheffer somyces cell, a Schizosaccharomycescell, a Sporidiobolus cell, a Torula cell, a Torulaspora cell, a Trichosporon cell, a Wickerhamomyces cell, a Yarrowia cell, and a Zygosaccharomyces cell. The cell of embodiment 16, wherein the yeast cell is selected from the group consisting of an Arxula adeninivorans cell, an Aureobasidium melanogenum cell, aBrettanomyces bruxellensis cell, a Candida albicans cell, a Candida antarctica cell, a Candida auris cell, a Candida blankii cell, a Candida dubliniensis cell, a Candida glabrata cell, a Candida humilis cell, a Candida krusei cell, a Candida lusitaniae cell, a Candida oleophila cell, a Candida parapsilosis cell, a Candida stellata cell, a Candida telluris cell, a Candida tropicalis cell, a Candida viswanathii cell, a Cryotpococcus gattii cell, a Cryotpococcus neoformans cell, aDekkera anomala cell, an Eremothecium gossypii cell, a Geotrichum candidum cell, a Kluyveromyces lactis cell, a Kluyveromyces marxianus cell, a Komagataella pastoris cell, a Lachancea kluyveri cell, a Leucosporidium frigidum cell, aMeyerozyma guiliermondii cell, an Ogataea polymorpha cell, a Rhodotorula glutinis cell, a Rhodotorula mucilaginosa cell, a Rhodotorula rubra cell, a Saccharomyces bayanus cell, a Saccharomyces boulardii cell, a Saccharomyces exiguus cell, a Saccharomyces florentinus cell, a Saccharomyces pastorianus cell, a Saccharomyces telluris cell, a Saccharomyces uvarum cell, a Scheffer somyces stipitis cell, a Schizosaccharomyces pombe cell, a Sporidiobolus salmonicolor cell, a Torulaspora delbrueckii cell, a Torulaspora globosa cell, a Trichosporon asteroides cell, a Trichosporon mycotoxinovorans cell, a Wickerhamomyces anomalus cell, a Yarrowia lipolytica cell, a Zygosaccharomyces bailii cell, and a Zygosaccharomyces bayanus cell. The cell of embodiment 15, wherein the cell is a prokaryotic cell. The cell of embodiment 20, wherein the prokaryotic cell is selected from the group consisting of an Escherichia cell, aBacillus cell, a Pseudomonas cell, and a Corynebacterium cell. The cell of embodiment 15, wherein the cell is a plant cell. The cell of embodiment 15, wherein the cell is an animal cell. A cell comprising a heterologous polypeptide, or a nucleic acid molecule encoding the heterologous polypeptide, wherein the heterologous polypeptide comprises an amino acid sequence at least 80% identical or similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5 or 8 to 12.The cell of embodiment 24, wherein the cell produces an increased ratio of geranyl pyrophosphate (GPP) to famesyl pyrophosphate (FPP) as compared to a control cell grown under comparable conditions. The cell of embodiment 25, wherein the increased ratio of GPP to FPP comprises a GPP increase of at least 5% as compared to the control cell. The cell of embodiment 25 or embodiment 26, wherein the increased ratio of GPP to FPP comprises an FPP decrease of at least 5% as compared to the control cell. The cell of embodiment 24, wherein the cell produces an increased ratio of geranyl pyrophosphate (GPP) derivative to famesyl pyrophosphate (FPP) derivative as compared to a control cell grown under comparable conditions. The cell of embodiment 28, wherein the increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of at least 5% as compared to the control cell. The cell of embodiment 28 or embodiment 29, wherein the increased ratio of GPP derivative to FPP derivative comprises an FPP derivative decrease of at least 5% as compared to the control cell. The cell of embodiment 24, wherein the cell produces an increased ratio of geranyl pyrophosphate (GPP) plus GPP derivatives to famesyl pyrophosphate (FPP) plus FPP derivatives as compared to a control cell grown under comparable conditions. The cell of embodiment 31, wherein the increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises an increase of GPP plus GPP derivative of at least 5% as compared to the control cell. The cell of embodiment 31 or embodiment 32, wherein the increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a decrease of FPP plus FPP derivative of at least 5% as compared to the control cell. The cell of any one of embodiments 24 to 33, wherein the nucleic acid molecule encoding the heterologous polypeptide is operably linked to a promoter. The cell of embodiment 34, wherein the promoter is a constitutive promoter.The cell of embodiment 35, wherein the constitutive promoter is selected from the group consisting of a glyceraldehyde-3-phosphate dehydrogenase (TDH3) promoter, a triose phosphate isomerase (TPI1) promoter, an enolase 2 (EN02) promoter, an alcohol dehydrogenase (ADH1) promoter, and a translational elongation factor EFl-a promoter. The cell of embodiment 34, wherein the promoter is an inducible promoter. The cell of embodiment 37, wherein the inducible promoter is selected from the group consisting of a temperature-inducible promoter and a chemically inducible promoter. The cell of any one of embodiments 24 to 38, wherein the nucleic acid molecule encoding the heterologous polypeptide is operably linked to an enhancer element. The cell of any one of embodiments 24 to 39, wherein the cell is a yeast cell. The cell of embodiment 40, wherein the yeast cell is a Saccharomyces cerevisiae cell. The cell of embodiment 40, wherein the yeast cell is selected from the group consisting of an Arxula cell, anAureobasidium cell, aBrettanomyces cell, a Candida cell, a Cryotpococcus cell, a Dekkera cell, an Eremothecium cell, a Geotrichum cell, a Kluyveromyces cell, a Komagataella cell, a Lachancea cell, a Leucosporidium cell, aMeyerozyma cell, an Ogataea cell, aRhodotorula cell, a Saccharomyces cell, a Scheffer somyces cell, a Schizosaccharomyces cell, a Sporidiobolus cell, a Torula cell, a Torulaspora cell, a Trichosporon cell, a Wickerhamomyces cell, a Yarrowia cell, and a Zygosaccharomyces cell. The cell of embodiment 40, wherein the yeast cell is selected from the group consisting of an Arxula adeninivorans cell, anAureobasidium melanogenum cell, aBrettanomyces bruxellensis cell, a Candida albicans cell, a Candida antarctica cell, a Candida auris cell, a Candida blankii cell, a Candida dubliniensis cell, a Candida glabrata cell, a Candida humilis cell, a Candida krusei cell, a Candida lusitaniae cell, a Candida oleophila cell, a Candida parapsilosis cell, a Candida stellata cell, a Candida telluris cell, a Candida tropicalis cell, a Candida viswanathii cell, a Cryotpococcus gattii cell, a Cryotpococcus neoformans cell, a Dekkera anomala cell, an Eremothecium gossypii cell, a Geotrichum candidum cell, a Kluyveromyces lactis cell, a Kluyveromyces marxianus cell, a Komagataella pastoris cell, a Lachancea kluyveri cell, a Leucosporidium frigidum cell, aMeyerozyma guiliermondii cell, an Ogataea polymorpha cell, a Rhodotorula glutinis cell, a Rhodotorula mucilaginosa cell, a Rhodotorula rubra cell, aSaccharomyces bayanus cell, a Saccharomyces boulardii cell, a Saccharomyces exiguus cell, a Saccharomyces florentinus cell, a Saccharomyces pastorianus cell, a Saccharomyces telluris cell, a Saccharomyces uvarum cell, a Scheffer somyces stipitis cell, a Schizosaccharomyces pombe cell, a Sporidiobolus salmonicolor cell, a Torulaspora delbrueckii cell, a Torulaspora globosa cell, a Trichosporon asteroides cesll, a Trichosporon mycotoxinovorans cell, a Wickerhamomyces anomalus cell, a Yarrowia lipolytica cell, a Zygosaccharomyces bailii cell, and a Zygosaccharomyces bayanus cell. The cell of any one of embodiments 24 to 38, wherein the cell is a prokaryotic cell. The cell of embodiment 44, wherein the prokaryotic cell is selected from the group consisting of an Escherichia cell, a Bacillus cell, a Pseudomonas cell, and a Corynebacterium cell. The cell of any one of embodiments 24 to 38, wherein the cell is a plant cell. The cell of any one of embodiments 24 to 38, wherein the cell is an animal cell. A chimeric protein, wherein the chimeric protein comprises a first portion comprising at least 10 amino acid residues that are identical to an amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7 and a second portion comprising at least 10 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12, wherein the chimeric protein produces a higher GPP to FPP ratio than at least one of SEQ ID NOs: 6 to 12 when the chimeric protein is active in a cell. The chimeric protein of embodiment 48, wherein the first portion is positioned on the aminoterminus side of the second portion. The chimeric protein of embodiment 48, wherein the first portion is positioned on the carboxyterminus side of the second portion. The chimeric protein of any one of embodiments 48 to 50, wherein the chimeric protein further comprises a third portion, wherein the third portion comprises at least 10 amino acid residues. The chimeric protein of embodiment 51, wherein the third portion is positioned at the aminoterminus of the chimeric protein. The chimeric protein of embodiment 51, wherein the third portion is positioned at the carboxyterminus of the chimeric protein.A nucleic acid molecule comprising a polynucleotide sequence encoding the chimeric protein of any one of embodiments 48 to 53. The nucleic acid molecule of embodiment 54, wherein the polynucleotide sequence is operably linked to a promoter. The nucleic acid molecule of embodiment 55, wherein the promoter is a constitutive promoter. The nucleic acid molecule of embodiment 56, wherein the constitutive promoter is selected from the group consisting of a glyceraldehyde-3-phosphate dehydrogenase (TDH3) promoter, a triose phosphate isomerase (TPI1) promoter, an enolase 2 (EN02) promoter, an alcohol dehydrogenase (ADH1) promoter, and a translational elongation factor EFl-a promoter. The nucleic acid molecule of embodiment 55, wherein the promoter is an inducible promoter. The nucleic acid molecule of embodiment 58, wherein the inducible promoter is selected from the group consisting of a temperature-inducible promoter and a chemically inducible promoter. The nucleic acid molecule of any one of embodiments 54 to 59, wherein the polynucleotide sequence is operably linked to an enhancer element. A cell comprising the chimeric protein of any one of embodiments 48 to 53. A cell comprising the nucleic acid molecule of any one of embodiments 54 to 60. The cell of embodiment 61 or embodiment 62, wherein the cell is a yeast cell. The cell of embodiment 63, wherein the yeast cell is a Saccharomyces cerevisiae cell. The cell of embodiment 63, wherein the yeast cell is selected from the group consisting of an Arxula cell, anAureobasidium cell, aBrettanomyces cell, a Candida cell, a Cryotpococcus cell, a Dekkera cell, an Eremothecium cell, a Geotrichum cell, a Kluyveromyces cell, a Komagataella cell, a Lachancea cell, a Leucosporidium cell, aMeyerozyma cell, an Ogataea cell, aRhodotorula cell, a Saccharomyces cell, a Scheffer somyces cell, a Schizosaccharomyces cell, a Sporidiobolus cell, a Torula cell, a Torulaspora cell, a Trichosporon cell, a Wickerhamomyces cell, a Yarrowia cell, and a Zygosaccharomyces cell. The cell of embodiment 63, wherein the yeast cell is selected from the group consisting of anArxula adeninivorans cell, anAureobasidium melanogenum cell, aBrettanomyces bruxellensiscell, a Candida albicans cell, a Candida antarctica cell, a Candida auris cell, a Candida blankii cell, a Candida dubliniensis cell, a Candida glabrata cell, a Candida humilis cell, a Candida krusei cell, a Candida lusitaniae cell, a Candida oleophila cell, a Candida parapsilosis cell, a Candida stellata cell, a Candida telluris cell, a Candida tropicalis cell, a Candida viswanathii cell, a Cryotpococcus gattii cell, a Cryotpococcus neoformans cell, aDekkera anomala cell, an Eremothecium gossypii cell, a Geotrichum candidum cell, a Kluyveromyces lactis cell, a Kluyveromyces marxianus cell, a Komagataella pastoris cell, a Lachancea kluyveri cell, a Leucosporidium frigidum cell, aMeyerozyma guiliermondii cell, an Ogataea polymorpha cell, a Rhodotorula glutinis cell, a Rhodotorula mucilaginosa cell, a Rhodotorula rubra cell, a Saccharomyces bayanus cell, a Saccharomyces boulardii cell, a Saccharomyces exiguus cell, a Saccharomyces florentinus cell, a Saccharomyces pastorianus cell, a Saccharomyces telluris cell, a Saccharomyces uvarum cell, a Scheffer somyces stipitis cell, a Schizosaccharomyces pombe cell, a Sporidiobolus salmonicolor cell, a Torulaspora delbrueckii cell, a Torulaspora globosa cell, a Trichosporon asteroides cesll, a Trichosporon mycotoxinovorans cell, a Wickerhamomyces anomalus cell, a Yarrowia lipolytica cell, a Zygosaccharomyces bailii cell, and a Zygosaccharomyces bayanus cell. The cell of embodiment 61 or embodiment 62, wherein the cell is a prokaryotic cell. The cell of embodiment 67, wherein the prokaryotic cell is selected from the group consisting of an Escherichia cell, aBacillus cell, a Pseudomonas cell, and a Corynebacterium cell. The cell of embodiment 61 or embodiment 62, wherein the cell is a plant cell. The cell of embodiment 61 or embodiment 62, wherein the cell is an animal cell. A method of generating geranyl pyrophosphate (GPP) or a GPP-derivative in a cell, the method comprising:(a) providing a recombinant DNA construct to the cell, wherein the recombinant DNA construct comprises a promoter operably linked to a nucleic acid molecule encoding a heterologous polypeptide at least 80% identical or similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5 or 8 to 12; and(b) providing appropriate growth conditions for the cell, thereby allowing the cell to generate the GPP or GPP-derivative.A method of generating geranyl pyrophosphate (GPP) or a GPP-derivative in a cell, the method comprising:(a) providing a recombinant DNA construct to the cell, wherein the recombinant DNA construct comprises a promoter operably linked to a nucleic acid molecule encoding a chimeric protein, wherein the chimeric protein comprises a first portion comprising at least 10 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7 and a second portion comprising at least 10 amino acid residues that are identical to the amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12; and(b) providing appropriate growth conditions for the cell, thereby allowing the cell to generate the GPP or GPP-derivative. The method of embodiment 71 or embodiment 72, wherein the GPP-derivative is selected from the group consisting of geraniol, limonene, / tipinene, a-pinene. / i-phellandrene. sabinene, perillyl alcohol, linalool, a-terpineol, and nerol. The method of embodiment 72, wherein the first portion is positioned on the amino-terminus side of the second portion. The method of embodiment 72, wherein the first portion is positioned in the carboxy-terminus side of the second portion. The method of any one of embodiments 72 to 75, wherein the chimeric protein further comprises a third portion, wherein the third portion comprises at least 10 amino acids. The method of embodiment 76, wherein the third portion is positioned at the amino-terminus of the chimeric protein. The method of embodiment 76, wherein the third portion is positioned at the carboxy-terminus of the chimeric protein. The method of any one of embodiments 71 to 78, wherein the promoter is a constitutive promoter. The method of embodiment 79, wherein the constitutive promoter is selected from the group consisting of a glyceraldehyde-3-phosphate dehydrogenase (TDH3) promoter, a triosephosphate isomerase (TPI1) promoter, an enolase 2 (EN02) promoter, an alcohol dehydrogenase (ADH1) promoter, and a translational elongation factor EFl-a promoter. The method of any one of embodiments 71 to 78, wherein the promoter is an inducible promoter. The method of embodiment 81, wherein the inducible promoter is selected from the group consisting of a temperature-inducible promoter and a chemically inducible promoter. The method of any one of embodiments 71 to 82, wherein the nucleic acid molecule is operably linked to an enhancer element. The method of any one of embodiments 71 to 83, wherein the cell is a yeast cell. The method of embodiment 84, wherein the yeast cell is a Saccharomyces cerevisiae cell. The method of embodiment 84, wherein the yeast cell is selected from the group consisting of an Arxula cell, an Aureobasidium cell, aBrettanomyces cell, a Candida cell, a Cryotpococcus cell, aDekkera cell, an Eremothecium cell, a Geotrichum cell, a Kluyveromyces cell, a Komagataella cell, aLachancea cell, a Leucosporidium cell, aMeyerozyma cell, an Ogataea cell, aRhodotorula cell, a Saccharomyces cell, a Scheffersomyces cell, a Schizosaccharomyces cell, a Sporidiobolus cell, a Torula cell, a Torulaspora cell, a Trichosporon cell, a Wickerhamomyces cell, a Yarrowia cell, and a Zygosaccharomyces cell. The method of embodiment 84, wherein the yeast cell is selected from the group consisting of a Arxula adeninivorans cell, an Aureobasidium melanogenum cell, aBrettanomyces bruxellensis cell, a Candida albicans cell, a Candida antarctica cell, a Candida auris cell, a Candida blankii cell, a Candida dubliniensis cell, a Candida glabrata cell, a Candida humilis cell, a Candida krusei cell, a Candida lusitaniae cell, a Candida oleophila cell, a Candida parapsilosis cell, a Candida stellata cell, a Candida telluris cell, a Candida tropicalis cell, a Candida viswanathii cell, a Cryotpococcus gattii cell, a Cryotpococcus neoformans cell, a Dekkera anomala cell, an Eremothecium gossypii cell, a Geotrichum candidum cell, a Kluyveromyces lactis cell, a Kluyveromyces marxianus cell, a Komagataella pastoris cell, a Lachancea kluyveri cell, a Leucosporidium frigidum cell, aMeyerozyma guiliermondii cell, an Ogataea polymorpha cell, aRhodotorula glutinis cell, aRhodotorula mucilaginosa cell, a Rhodotorula rubra cell, a Saccharomyces bayanus cell, a Saccharomyces boulardii cell, aSaccharomyces exiguus cell, a Saccharomyces florentinus cell, a Saccharomyces pastorianus cell, a Saccharomyces telluris cell, a Saccharomyces uvarum cell, a Scheffersomyces stipitis cell, a Schizosaccharomyces pombe cell, a Sporidiobolus salmonicolor cell, a Torulaspora delbrueckii cell, a Torulaspora globosa cell, a Trichosporon asteroides cesll, a Trichosporon mycotoxinovorans cell, a Wickerhamomyces anomalus cell, a Yarrowia lipolytica cell, a Zygosaccharomyces bailii cell, and a Zygosaccharomyces bayanus cell. The method of any one of embodiments 71 to 83, wherein the cell is a prokaryotic cell. The method of embodiment 88, wherein the prokaryotic cell is selected from the group consisting of an Escherichia cell, a Bacillus cell, a Pseudomonas cell, and a Corynebacterium cell. The method of any one of embodiments 71 to 83, wherein the cell is a plant cell. The method of any one of embodiments 71 to 83, wherein the cell is an animal cell. A method of modifying a cell, the method comprising:(a) providing to the cell:(i) a nucleic acid-guided nuclease, or a polynucleotide encoding the nucleic acid- guided nuclease; and(ii) at least one guide nucleic acid molecule, or a polynucleotide encoding the at least one guide nucleic acid molecule, wherein the at least one guide nucleic acid molecule is at least 80% identical or complementary to a gene encoding a geranyl pyrophosphate (GPP) synthase; and(b) providing the cell with conditions that allow the nucleic acid-guided nuclease and the at least one guide nucleic acid molecule to edit the gene encoding the GPP synthase to create a modified cell comprising a modified GPP synthase. The method of embodiment 92, wherein step (a) further comprises providing the cell with(iii) at least one donor template, or a polynucleotide encoding the at least one donor template. The method of embodiment 92 or embodiment 93, wherein the modified cell exhibits increased production of GPP as compared to a control cell comprises an unmodified GPP synthase.

[0133] Having now generally described the disclosure, the same will be more readily understood through reference to the following examples that are provided by way of illustration, and are not intended to be limiting of the present disclosure, unless specified.EXAMPLESExample 1. Creation of yeast strains expressing a heterologous GPP synthase

[0134] A truncated geraniol synthase from Catharanthus roseus is integrated into various Saccharomyces cerevisiae strains using techniques standard in the art. See, for example, Jiang et al., Metab Eng. , 41 : 57-66 (May 2017). Because GPP is rapidly converted to FPP, geraniol synthase activity, which converts GPP to the readily quantified molecule geraniol, can serve as a proxy for GPP flux in cells.

[0135] The 5. cerevisiae strains with an integrated geraniol synthase are further modified to comprise different homologues of GPP synthases (e.g., ERG20) from different species and are described in Table 2.Table 2. Yeast strains with heterologous GPP synthase (GPPS) homologues

[0136] The ERG20 variant, ERG20WW, has exhibited higher GPP flux than ERG20, and has exhibited the highest published GPP flux. See, for example, Jiang et al. (May 2017).

[0137] The yeast strains are grown under suitable conditions to allow for the activity of GPP synthases and the production of geraniol.

[0138] As shown in the upper panel of Fig. 1, which depicts the amount of geraniol observed in mg / L, STR1408 exhibits a higher GPP flux than STR1205, which expresses ERG20WW. Additionally, each of strains STR1406, STR1407, STR108, STR1506, and STR1507 exhibit a higher GPP flux than STR1200, which expresses the wildtype ERG20.

[0139] The lower panel of Fig. 1 depicts the optical density of each strain culture. Because each strain has a similar optical density, it is not believed that the presence of a heterologous GPPS gene negatively impacts the growth of 5. cerevisiae.Example 2. Creation of an EG20WW variant yeast strain

[0140] As described in Example 1, S. cerevisiae strains comprising a truncated C. roseus geraniol synthase are generated. STR1200 comprises wildtype ERG20 (SEQ ID NOs: 6 and 18). STR1342 comprises ERG20WW (SEQ ID NOs: 7 and 19). STR1633 comprises an ERG20WW variant that comprises a 30 amino acid residue extension (SEQ ID NOs: 1 and 13).

[0141] The yeast strains are grown under suitable conditions to allow for the activity of GPP synthases and the production of geraniol.

[0142] As shown in Fig. 2, which depicts the amount of geraniol observed in mg / L, STR1633 exhibits a higher GPP flux than both ERG20 and ERG20WW.Example 3. Creation of chimeric GPP synthases

[0143] As described in Example 1, S. cerevisiae strains comprising a truncated C. roseus geraniol synthase are generated. STR2247 comprises ERG20WW (SEQ ID NOs: 7 and 19).

[0144] STR2301 comprises a GPPS with an N-terminus comprising amino acid residues 1 to15 of L. erythrorhizon GPPS (SEQ ID NO: 10) followed by amino acid residues 16 to 352 of ERG20WW (SEQ ID NO: 7). The chimeric GPPS in STR2301 is provided as SEQ ID NOs: 2 and 14.

[0145] STR2302 comprises a GPPS with an N-terminus comprising amino acid residues 1 to15 of L. erythrorhizon GPPS (SEQ ID NO: 10) followed by amino acid residues 16 to 352 of ERG20WW (SEQ ID NO: 7) and the 30 amino acid residue extension that is present in SEQ ID NO: 1. The chimeric GPPS in STR2302 is provided as SEQ ID NOs: 3 and 15.

[0146] STR2318 comprises a GPPS with an N-terminus comprising amino acid residues 1 to255 of ERG20WW (SEQ ID NO: 7) followed by amino acid residues 256 to 350 of L. erythrorhizon GPPS (SEQ ID NO: 10). The chimeric GPPS in STR2318 is provided as SEQ ID NOs: 4 and 16.

[0147] STR2320 comprises a GPPS with an N-terminus comprising amino acid residues 1 to280 of ERG20WW (SEQ ID NO: 7) followed by amino acid residues 281 to 350 of L. erythrorhizon GPPS (SEQ ID NO: 10). The chimeric GPPS in 2320 is provided as SEQ ID NOs: 5 and 17.

[0148] The yeast strains are grown under suitable conditions to allow for the activity of GPP synthases and the production of geraniol.

[0149] As shown in Fig. 3, which depicts the amount of geraniol observed in mg / L, each of STR2301, STR2302, STR2318, and STR2320 exhibit increased geraniol production as compared to the control strain STR2247.

Claims

CLAIMS1. A polypeptide comprising an amino acid sequence at least 80% identical or similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5.

2. A nucleic acid molecule comprising a polynucleotide sequence encoding the polypeptide of claim 1.

3. The nucleic acid molecule of claim 2, wherein the polynucleotide sequence is at least 80% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 13 to 17.

4. The nucleic acid molecule of claim 2, wherein the polynucleotide sequence is operably linked to a promoter.

5. The nucleic acid molecule of claim 4, wherein the promoter is a constitutive promoter.

6. The nucleic acid molecule of claim 5, wherein the constitutive promoter is selected from the group consisting of a glyceraldehyde-3 -phosphate dehydrogenase (TDH3) promoter, a triose phosphate isomerase (TPI1) promoter, an enolase 2 (ENO2) promoter, an alcohol dehydrogenase (ADH1) promoter, and a translational elongation factor EFl -a promoter.

7. The nucleic acid molecule of claim 4, wherein the promoter is an inducible promoter.

8. The nucleic acid molecule of claim 7, wherein the inducible promoter is selected from the group consisting of a temperature-inducible promoter and a chemically-inducible promoter.

9. The nucleic acid molecule of any one of claims 2 to 8, wherein the polynucleotide sequence is operably linked to an enhancer element.

10. The nucleic acid molecule of any one of claims 2 to 9, wherein the polynucleotide sequence is codon optimized for a fungal cell.

11. The nucleic acid molecule of any one of claims 2 to 9, wherein the polynucleotide sequence is codon optimized for a prokaryotic cell.

12. The nucleic acid molecule of any one of claims 2 to 9, wherein the polynucleotide sequence is codon optimized for a plant cell.

13. The nucleic acid molecule of any one of claims 2 to 9, wherein the polynucleotide sequence is codon optimized for an animal cell.

14. The nucleic acid molecule of any one of claims 2 to 13, wherein the nucleic acid molecule is within a vector.

15. A cell comprising the polypeptide of claim 1 or the nucleic acid molecule of any one of claims 2 to 14.

16. The cell of claim 15, wherein the cell is a yeast cell.

17. The cell of claim 16, wherein the yeast cell is a Saccharomyces cerevisiae cell.

18. The cell of claim 16, wherein the yeast cell is selected from the group consisting of an Arxula cell, an Aureobasidium cell, a Brettanomyces cell, a Candida cell, a Cryotpococcus cell, a Dekkera cell, an Eremothecium cell, a Geotrichum cell, a Kluyveromyces cell, a Komagataella cell, aLachancea cell, a Leucosporidium cell, aMeyerozyma cell, an Ogataea cell, aRhodotorula cell, a Saccharomyces cell, a Scheffersomyces cell, a Schizosaccharomyces cell, a Sporidiobolus cell, a Torula cell, a Torulaspora cell, a Trichosporon cell, a Wickerhamomyces cell, a Yarrowia cell, and a Zygosaccharomyces cell.

19. The cell of claim 16, wherein the yeast cell is selected from the group consisting of an Arxula adeninivorans cell, an Aureobasidium melanogenum cell, a Brettanomyces bruxellensis cell, a Candida albicans cell, a Candida antarctica cell, a Candida auris cell, a Candida blankii cell, a Candida dubliniensis cell, a Candida glabrata cell, a Candida humilis cell, a Candida krusei cell, a Candida lusitaniae cell, a Candida oleophila cell, a Candida parapsilosis cell, a Candida stellata cell, a Candida telluris cell, a Candida tropicalis cell, a Candida viswanathii cell, a Cryotpococcus gattii cell, a Cryotpococcus neoformans cell, a Dekkera anomala cell, an Eremothecium gossypii cell, a Geotrichum candidum cell, a Kluyveromyces lactis cell, a Kluyveromyces marxianus cell, a Komagataella pastoris cell, a Lachancea kluyveri cell, a Leucosporidium frigidum cell, aMeyerozyma guiliermondii cell, an Ogataea polymorpha cell, aRhodotorula glutinis cell, aRhodotorula mucilaginosa cell, aRhodotorula rubra cell, a Saccharomyces bayanus cell, a Saccharomyces boulardii cell, a Saccharomyces exiguus cell, a Saccharomyces florentinus cell, a Saccharomyces pastorianus cell, a Saccharomyces telluris cell, a Saccharomyces uvarum cell, a Scheffersomyces stipitis cell, a Schizosaccharomyces pombe cell, a Sporidiobolus salmonicolor cell, a Torulasporadelbrueckii cell, a Torulaspora globosa cell, a Trichosporon asteroides cell, a Trichosporon mycotoxinovorans cell, a Wickerhamomyces anomalus cell, a Yarrowia lipolytica cell, a Zygosaccharomyces bailii cell, and a Zygosaccharomyces bayanus cell.

20. The cell of claim 15, wherein the cell is a prokaryotic cell.

21. The cell of claim 20, wherein the prokaryotic cell is selected from the group consisting of an Escherichia cell, a Bacillus cell, a Pseudomonas cell, and a Corynebacterium cell.

22. The cell of claim 15, wherein the cell is a plant cell.

23. The cell of claim 15, wherein the cell is an animal cell.

24. A cell comprising a heterologous polypeptide, or a nucleic acid molecule encoding the heterologous polypeptide, wherein the heterologous polypeptide comprises an amino acid sequence at least 80% identical or similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5 or 8 to 12.

25. The cell of claim 24, wherein the cell produces an increased ratio of geranyl pyrophosphate (GPP) to famesyl pyrophosphate (FPP) as compared to a control cell grown under comparable conditions.

26. The cell of claim 25, wherein the increased ratio of GPP to FPP comprises a GPP increase of at least 5% as compared to the control cell.

27. The cell of claim 25 or 26, wherein the increased ratio of GPP to FPP comprises an FPP decrease of at least 5% as compared to the control cell.

28. The cell of claim 24, wherein the cell produces an increased ratio of geranyl pyrophosphate (GPP) derivative to famesyl pyrophosphate (FPP) derivative as compared to a control cell grown under comparable conditions.

29. The cell of claim 28, wherein the increased ratio of GPP derivative to FPP derivative comprises a GPP derivative increase of at least 5% as compared to the control cell.

30. The cell of claim 28 or 29, wherein the increased ratio of GPP derivative to FPP derivative comprises an FPP derivative decrease of at least 5% as compared to the control cell.

31. The cell of claim 24, wherein the cell produces an increased ratio of geranyl pyrophosphate (GPP) plus GPP derivatives to famesyl pyrophosphate (FPP) plus FPP derivatives as compared to a control cell grown under comparable conditions.

32. The cell of claim 31, wherein the increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises an increase of GPP plus GPP derivative of at least 5% as compared to the control cell.

33. The cell of claim 31 or 32, wherein the increased ratio of GPP plus GPP derivative to FPP plus FPP derivative comprises a decrease of FPP plus FPP derivative of at least 5% as compared to the control cell.

34. The cell of any one of claims 24 to 33, wherein the nucleic acid molecule encoding the heterologous polypeptide is operably linked to a promoter.

35. The cell of claim 34, wherein the promoter is a constitutive promoter.

36. The cell of claim 35, wherein the constitutive promoter is selected from the group consisting of a glyceraldehyde-3 -phosphate dehydrogenase (TDH3) promoter, a triose phosphate isomerase (TPI1) promoter, an enolase 2 (EN02) promoter, an alcohol dehydrogenase (ADH1) promoter, and a translational elongation factor EFl-a promoter.

37. The cell of claim 34, wherein the promoter is an inducible promoter.

38. The cell of claim 37, wherein the inducible promoter is selected from the group consisting of a temperature-inducible promoter and a chemically inducible promoter.

39. The cell of any one of claims 24 to 38, wherein the nucleic acid molecule encoding the heterologous polypeptide is operably linked to an enhancer element.

40. The cell of any one of claims 24 to 39, wherein the cell is a yeast cell.

41. The cell of claim 40, wherein the yeast cell is a Saccharomyces cerevisiae cell.

42. The cell of claim 40, wherein the yeast cell is selected from the group consisting of an Arxula cell, an Aureobasidium cell, a Brettanomyces cell, a Candida cell, a Cryotpococcus cell, a Dekkera cell, an Eremothecium cell, a Geotrichum cell, a Kluyveromyces cell, a Komagataella cell, aLachancea cell, a Leucosporidium cell, a Meyerozyina cell, an Ogataeacell, aRhodotorula cell, a Saccharomyces cell, a Scheffer somyces cell, aSchizosaccharomyces cell, a Sporidiobolus cell, a Torula cell, a Torulaspora cell, a Trichosporon cell, a Wickerhamomyces cell, a Yarrowia cell, and a Zygosaccharomyces cell.

43. The cell of claim 40, wherein the yeast cell is selected from the group consisting of an Arxula adeninivorans cell, an Aureobasidium melanogenum cell, a Brettanomyces bruxellensis cell, a Candida albicans cell, a Candida antarctica cell, a Candida auris cell, a Candida blankii cell, a Candida dubliniensis cell, a Candida glabrata cell, a Candida humilis cell, a Candida krusei cell, a Candida lusitaniae cell, a Candida oleophila cell, a Candida parapsilosis cell, a Candida stellata cell, a Candida telluris cell, a Candida tropicalis cell, a Candida viswanathii cell, a Cryotpococcus gattii cell, a Cryotpococcus neoformans cell, a Dekker a anomala cell, an Eremothecium gossypii cell, a Geotrichum candidum cell, a Kluyveromyces lactis cell, a Kluyveromyces marxianus cell, a Komagataella pastoris cell, a Lachancea kluyveri cell, a Leucosporidium frigidum cell, aMeyerozyma guiliermondii cell, an Ogataea polymorpha cell, aRhodotorula glutinis cell, aRhodotorula mucilaginosa cell, aRhodotorula rubra cell, a Saccharomyces bayanus cell, a Saccharomyces boulardii cell, a Saccharomyces exiguus cell, a Saccharomyces florentinus cell, a Saccharomyces pastorianus cell, a Saccharomyces telluris cell, a Saccharomyces uvarum cell, a Scheffersomyces stipitis cell, a Schizosaccharomyces pombe cell, a Sporidiobolus salmonicolor cell, a Torulaspora delbrueckii cell, a Torulaspora globosa cell, a Trichosporon asteroides cesll, a Trichosporon mycotoxinovorans cell, a Wickerhamomyces anomalus cell, a Yarrowia lipolytica cell, a Zygosaccharomyces bailii cell, and a Zygosaccharomyces bayanus cell.

44. The cell of any one of claims 24 to 38, wherein the cell is a prokaryotic cell.

45. The cell of claim 44, wherein the prokaryotic cell is selected from the group consisting of an Escherichia cell, a Bacillus cell, a Pseudomonas cell, and a Corynebacterium cell.

46. The cell of any one of claims 24 to 38, wherein the cell is a plant cell.

47. The cell of any one of claims 24 to 38, wherein the cell is an animal cell.

48. A chimeric protein, wherein the chimeric protein comprises a first portion comprising at least 10 amino acid residues that are identical to an amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7 and a second portion comprising at least 10 amino acid residues that are identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12, whereinthe chimeric protein produces a higher GPP to FPP ratio than at least one of SEQ ID NOs: 6 to 12 when the chimeric protein is active in a cell.

49. The chimeric protein of claim 48, wherein the first portion is positioned on the aminoterminus side of the second portion.

50. The chimeric protein of claim 48, wherein the first portion is positioned on the carboxyterminus side of the second portion.

51. The chimeric protein of any one of claims 48 to 50, wherein the chimeric protein further comprises a third portion, wherein the third portion comprises at least 10 amino acid residues.

52. The chimeric protein of claim 51, wherein the third portion is positioned at the aminoterminus of the chimeric protein.

53. The chimeric protein of claim 51, wherein the third portion is positioned at the carboxyterminus of the chimeric protein.

54. A nucleic acid molecule comprising a polynucleotide sequence encoding the chimeric protein of any one of claims 48 to 53.

55. The nucleic acid molecule of claim 54, wherein the polynucleotide sequence is operably linked to a promoter.

56. The nucleic acid molecule of claim 55, wherein the promoter is a constitutive promoter.

57. The nucleic acid molecule of claim 56, wherein the constitutive promoter is selected from the group consisting of a glyceraldehyde-3 -phosphate dehydrogenase (TDH3) promoter, a triose phosphate isomerase (TPI1) promoter, an enolase 2 (ENO2) promoter, an alcohol dehydrogenase (ADH1) promoter, and a translational elongation factor EFl -a promoter.

58. The nucleic acid molecule of claim 55, wherein the promoter is an inducible promoter.

59. The nucleic acid molecule of claim 58, wherein the inducible promoter is selected from the group consisting of a temperature-inducible promoter and a chemically inducible promoter.

60. The nucleic acid molecule of any one of claims 54 to 59, wherein the polynucleotide sequence is operably linked to an enhancer element.

61. A cell comprising the chimeric protein of any one of claims 48 to 53.

62. A cell comprising the nucleic acid molecule of any one of claims 54 to 60.

63. The cell of claim 61 or 62, wherein the cell is a yeast cell.

64. The cell of claim 63, wherein the yeast cell is a Saccharomyces cerevisiae cell.

65. The cell of claim 63, wherein the yeast cell is selected from the group consisting of an Arxula cell, an Aureobasidium cell, a Brettanomyces cell, a Candida cell, a Cryotpococcus cell, a Dekkera cell, an Eremothecium cell, a Geotrichum cell, a Kluyveromyces cell, a Komagataella cell, aLachancea cell, a Leucosporidium cell, aMeyerozyma cell, an Ogataea cell, aRhodotorula cell, a Saccharomyces cell, a Scheffersomyces cell, a Schizosaccharomyces cell, a Sporidiobolus cell, a Torula cell, a Torulaspora cell, a Trichosporon cell, a Wickerhamomyces cell, a Yarrowia cell, and a Zygosaccharomyces cell.

66. The cell of claim 63, wherein the yeast cell is selected from the group consisting of an Arxula adeninivorans cell, an Aureobasidium melanogenum cell, a Brettanomyces bruxellensis cell, a Candida albicans cell, a Candida antarctica cell, a Candida auris cell, a Candida blankii cell, a Candida dubliniensis cell, a Candida glabrata cell, a Candida humilis cell, a Candida krusei cell, a Candida lusitaniae cell, a Candida oleophila cell, a Candida parapsilosis cell, a Candida stellata cell, a Candida telluris cell, a Candida tropicalis cell, a Candida viswanathii cell, a Cryotpococcus gattii cell, a Cryotpococcus neoformans cell, a Dekkera anomala cell, an Eremothecium gossypii cell, a Geotrichum candidum cell, a Kluyveromyces lactis cell, a Kluyveromyces marxianus cell, a Komagataella pastoris cell, a Lachancea kluyveri cell, a Leucosporidium frigidum cell, aMeyerozyma guiliermondii cell, an Ogataea polymorpha cell, aRhodotorula glutinis cell, aRhodotorula mucilaginosa cell, aRhodotorula rubra cell, a Saccharomyces bayanus cell, a Saccharomyces boulardii cell, a Saccharomyces exiguus cell, a Saccharomyces florentinus cell, a Saccharomyces pastorianus cell, a Saccharomyces telluris cell, a Saccharomyces uvarum cell, a Scheffersomyces stipitis cell, a Schizosaccharomyces pombe cell, a Sporidiobolus salmonicolor cell, a Torulaspora delbrueckii cell, a Torulaspora globosa cell, a Trichosporon asteroides cesll, a Trichosporon mycotoxinovorans cell, a Wickerhamomyces anomalus cell, a Yarrowia lipolytica cell, a Zygosaccharomyces bailii cell, and a Zygosaccharomyces bayanus cell.

67. The cell of claim 61 or 62, wherein the cell is a prokaryotic cell.

68. The cell of claim 67, wherein the prokaryotic cell is selected from the group consisting of an Escherichia cell, a Bacillus cell, a Pseudomonas cell, and a Corynebacterium cell.

69. The cell of claim 61 or 62, wherein the cell is a plant cell.

70. The cell of claim 61 or 62, wherein the cell is an animal cell.

71. A method of generating geranyl pyrophosphate (GPP) or a GPP-derivative in a cell, the method comprising:(a) providing a recombinant DNA construct to the cell, wherein the recombinant DNA construct comprises a promoter operably linked to a nucleic acid molecule encoding a heterologous polypeptide at least 80% identical or similar to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5 or 8 to 12; and(b) providing appropriate growth conditions for the cell, thereby allowing the cell to generate the GPP or GPP-derivative.

72. A method of generating geranyl pyrophosphate (GPP) or a GPP-derivative in a cell, the method comprising:(a) providing a recombinant DNA construct to the cell, wherein the recombinant DNA construct comprises a promoter operably linked to a nucleic acid molecule encoding a chimeric protein, wherein the chimeric protein comprises a first portion comprising at least 10 amino acid residues that are identical to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7 and a second portion comprising at least 10 amino acid residues that are identical to the amino acid sequence selected from the group consisting of SEQ ID NOs: 8 to 12; and(b) providing appropriate growth conditions for the cell, thereby allowing the cell to generate the GPP or GPP-derivative.

73. The method of claim 71 or 72, wherein the GPP-derivative is selected from the group consisting of geraniol, limonene, / >-pinene. r / .-pinene. ^-phellandrene, sabinene, perilly 1 alcohol, linalool, a-terpineol, and nerol.

74. The method of claim 72, wherein the first portion is positioned on the amino-terminus side of the second portion.

75. The method of claim 72, wherein the first portion is positioned in the carboxy-terminus side of the second portion.

76. The method of any one of claims 72 to 75, wherein the chimeric protein further comprises a third portion, wherein the third portion comprises at least 10 amino acids.

77. The method of claim 76, wherein the third portion is positioned at the amino-terminus of the chimeric protein.

78. The method of claim 76, wherein the third portion is positioned at the carboxy -terminus of the chimeric protein.

79. The method of any one of claims 71 to 78, wherein the promoter is a constitutive promoter.

80. The method of claim 79, wherein the constitutive promoter is selected from the group consisting of a glyceraldehyde-3-phosphate dehydrogenase (TDH3) promoter, a triose phosphate isomerase (TPI1) promoter, an enolase 2 (ENO2) promoter, an alcohol dehydrogenase (ADH1) promoter, and a translational elongation factor EFl-a promoter.

81. The method of any one of claims 71 to 78, wherein the promoter is an inducible promoter.

82. The method of claim 81, wherein the inducible promoter is selected from the group consisting of a temperature-inducible promoter and a chemically inducible promoter.

83. The method of any one of claims 71 to 82, wherein the nucleic acid molecule is operably linked to an enhancer element.

84. The method of any one of claims 71 to 83, wherein the cell is a yeast cell.

85. The method of claim 84, wherein the yeast cell is a Saccharomyces cerevisiae cell.

86. The method of claim 84, wherein the yeast cell is selected from the group consisting of an Arxula cell, an Aureobasidium cell, aBrettanomyces cell, a Candida cell, a Cryotpococcus cell, a Dekker a cell, an Eremothecium cell, a Geotrichum cell, a Kluyveromyces cell, a Komagataella cell, aLachancea cell, a Leucosporidium cell, aMeyerozyma cell, an Ogataea cell, aRhodotorula cell, a Saccharomyces cell, a Scheffersomyces cell, a Schizosaccharomyces cell, a Sporidiobolus cell, a Torula cell, a Torulaspora cell, a Trichosporon cell, a Wickerhamomyces cell, a Yarrowia cell, and a Zygosaccharomyces cell.

87. The method of claim 84, wherein the yeast cell is selected from the group consisting of an Arxula adeninivorans cell, an Aureobasidium melanogenum cell, a Brettanomyces bruxellensis cell, a Candida albicans cell, a Candida antarctica cell, a Candida auris cell, a Candida blankii cell, a Candida dubliniensis cell, a Candida glabrata cell, a Candida humilis cell, a Candida krusei cell, a Candida lusitaniae cell, a Candida oleophila cell, a Candida parapsilosis cell, a Candida stellata cell, a Candida telluris cell, a Candida tropicalis cell, a Candida viswanathii cell, a Cryotpococcus gattii cell, a Cryotpococcus neoformans cell, a Dekkera anomala cell, an Eremothecium gossypii cell, a Geotrichum candidum cell, a Kluyveromyces lactis cell, a Kluyveromyces marxianus cell, a Komagataella pastoris cell, a Lachancea kluyveri cell, a Leucosporidium frigidum cell, Meyer ozyma guiliermondii cell, an Ogataea polymorpha cell, a Rhodotorula glutinis cell, a Rhodotorula mucilaginosa cell, a Rhodotorula rubra cell, a Saccharomyces bayanus cell, a Saccharomyces boulardii cell, a Saccharomyces exiguus cell, a Saccharomyces florentinus cell, a Saccharomyces pastorianus cell, a Saccharomyces telluris cell, a Saccharomyces uvarum cell, a Scheffersomyces stipitis cell, a Schizosaccharomyces pombe cell, a Sporidiobolus salmonicolor cell, a Torulaspora delbrueckii cell, a Torulaspora globosa cell, a Trichosporon asteroides cesll, a Trichosporon mycotoxinovorans cell, a Wickerhamomyces anomalus cell, a Yarrowia lipolytica cell, a Zygosaccharomyces bailii cell, and a Zygosaccharomyces bayanus cell.

88. The method of any one of claims 71 to 83, wherein the cell is a prokaryotic cell.

89. The method of claim 88, wherein the prokaryotic cell is selected from the group consisting of an Escherichia cell, a Bacillus cell, a Pseudomonas cell, and a Corynebacterium cell.

90. The method of any one of claims 71 to 83, wherein the cell is a plant cell.

91. The method of any one of claims 71 to 83, wherein the cell is an animal cell.

92. A method of modifying a cell, the method comprising:(a) providing to the cell:(i) a nucleic acid-guided nuclease, or a polynucleotide encoding the nucleic acid- guided nuclease; and(ii) at least one guide nucleic acid molecule, or a polynucleotide encoding the at least one guide nucleic acid molecule, wherein the at least one guide nucleicacid molecule is at least 80% identical or complementary to a gene encoding a geranyl pyrophosphate (GPP) synthase; and(b) providing the cell with conditions that allow the nucleic acid-guided nuclease and the at least one guide nucleic acid molecule to edit the gene encoding the GPP synthase to create a modified cell comprising a modified GPP synthase.

93. The method of claim 92, wherein step (a) further comprises providing the cell with (iii) at least one donor template, or a polynucleotide encoding the at least one donor template.

94. The method of claim 92 or 93, wherein the modified cell exhibits increased production of GPP as compared to a control cell that comprises an unmodified GPP synthase.

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