Phosphonopeptides and methods of making and use thereof

Abstract

Disclosed herein are compositions and methods of making and use thereof. For example, disclosed herein are compound defined by Formula I or a derivative or salt thereof. In some examples, the compound comprises AmPn-Arg-Val-DMA, AmPn-Ne-hydroxyarginine-Val-Ac, AmPn-Arg-Val-Ac, a derivative or salt thereof, or a combination thereof. In some examples, the compound is a Salinispora isolate or a derivative or salt thereof.

Description

[0001] PHOSPHONOPEPTIDES AND METHODS OF MAKING AND USE THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority to U.S. Provisional Application No. 63 / 575,011, filed April 5, 2024, which is hereby incorporated herein by reference in its entirety. STATEMENT OF GOVERNMENT SUPPORT This invention was made with government support under grant / contract no. R01 GM137135 awarded by the National Institutes of Health. The government has certain rights in the invention. BACKGROUND Some phosphonate natural products, including isolates from naturally-occurring microorganisms, have been shown to have inhibitory activities. The inhibitory activities underly their development as antibiotics and pesticides. Most bio-active phosphonate natural products have been isolated from Actinobacteria. Many plant, animal, and insect pathologies have poor or no modalities of control and new compositions are needed. The compositions and methods discussed herein address these and other needs. SUMMARY In accordance with the purposes of the disclosed compositions and methods as embodied and broadly described herein, the disclosed subject matter relates to compositions and methods of making and use thereof. For example, disclosed herein are compound defined by Formula I: I wherein R1is hydrogen, halide, substituted or unsubstituted C1-C20 alkyl, substituted or unsubstituted C3-C20cycloalkyl, substituted or unsubstituted C1-C20alkoxy, substituted or unsubstituted C3-C20aryl (e.g., substituted or unsubstituted phenyl), substituted or unsubstituted C4-C21 alkylaryl, NRxRy, or ORa; R2is hydrogen, halide, substituted or unsubstituted C1-C20 alkyl, substituted or unsubstituted C3-C20cycloalkyl, substituted or unsubstituted C1-C20alkoxy, substituted or unsubstituted C3-C20aryl (e.g., substituted or unsubstituted phenyl), substituted or unsubstituted C4-C21 alkylaryl, NRxRy, or ORb; R3is hydrogen, hydroxyl, halide, substituted or unsubstituted C1-C20alkyl, substituted or unsubstituted C1-C20acyl, substituted or unsubstituted C1-C20 alkoxy, substituted or unsubstituted C1-C20 amide, NRxRy, or one or more amino acids (e.g., one or more canonical or non-canonical amino acids); Raand Rbare each independently hydrogen, substituted or unsubstituted C1-C10alkyl, substituted or unsubstituted C3-C10aryl (e.g., substituted or unsubstituted phenyl), or substituted or unsubstituted C4-C11 alkylaryl; and Rxand Ryare independently selected from hydrogen, or substituted or unsubstituted C1-C5 alkyl, or substituted or unsubstituted C1-C5acyl; or a derivative or salt thereof. In some examples, R1is ORaand / or R2is ORb. In some examples, the compound is defined by Formula II: wherein R3is hydrogen, hydroxyl, halide, substituted or unsubstituted C1-C20alkyl, substituted or unsubstituted C1-C20acyl, substituted or unsubstituted C1-C20alkoxy, substituted or unsubstituted C1-C20 amide, NRxRy, or one or more amino acids (e.g., one or more canonical or non-canonical amino acids); Raand Rbare each independently hydrogen, substituted or unsubstituted C1-C10alkyl, substituted or unsubstituted C3-C10aryl (e.g., substituted or unsubstituted phenyl), or substituted or unsubstituted C4-C11 alkylaryl; and Rxand Ryare independently selected from hydrogen, or substituted or unsubstituted C1-C5 alkyl, or substituted or unsubstituted C1-C5acyl; or a derivative or salt thereof. In some examples, Raand / or Rbis hydrogen. In some examples, the compound is defined by Formula III: III wherein R3is hydrogen, hydroxyl, halide, substituted or unsubstituted C1-C20alkyl, substituted or unsubstituted C1-C20 acyl, substituted or unsubstituted C1-C20 alkoxy, substituted or unsubstituted C1-C20 amide, NRxRy, or one or more amino acids (e.g., one or more canonical or non-canonical amino acids); Rais hydrogen, substituted or unsubstituted C1-C10alkyl, substituted or unsubstituted C3-C10 aryl (e.g., substituted or unsubstituted phenyl), or substituted or unsubstituted C4-C11 alkylaryl; and Rxand Ryare independently selected from hydrogen, or substituted or unsubstituted C1-C5alkyl, or substituted or unsubstituted C1-C5acyl; or a derivative or salt thereof. In some examples, the compound is defined by Formula IV: IV wherein R3is hydrogen, hydroxyl, halide, substituted or unsubstituted C1-C20 alkyl, substituted or unsubstituted C1-C20acyl, substituted or unsubstituted C1-C20alkoxy, substituted or unsubstituted C1-C20 amide, NRxRy, or one or more amino acids (e.g., one or more canonical or non-canonical amino acids); and Rxand Ryare independently selected from hydrogen, or substituted or unsubstituted C1-C5alkyl, or substituted or unsubstituted C1-C5acyl; or a derivative or salt thereof. In some examples, R3is one or more amino acids (e.g., one or more canonical or non- canonical amino acids). In some examples, R3is one or more amino acids, each amino acid independently being selected from the group consisting of Arginine (Arg), Ne-hydroxyarginine, dehydro‐3‐methylaspartate, and Valine (Val). In some examples, the compound is defined by Formula V: wherein R4and R5are each independently hydrogen, hydroxyl, halide, substituted or unsubstituted C1-C20 alkyl, substituted or unsubstituted C1-C20 acyl, substituted or unsubstituted C1-C20 alkoxy, substituted or unsubstituted C1-C20 amide, NRxRy, or one or more amino acids (e.g., one or more canonical or non-canonical amino acids); and Rxand Ryare independently selected from hydrogen, or substituted or unsubstituted C1-C5 alkyl, or substituted or unsubstituted C1-C5 acyl; or a derivative or salt thereof. In some examples, R4and R5are each independently one or more amino acids (e.g., one or more canonical or non-canonical amino acids), or a derivative or salt thereof. In some examples, R4and R5are each independently one or more amino acids, each amino acid independently being selected from the group consisting of Arginine (Arg), Ne-hydroxyarginine, dehydro‐3‐methylaspartate, and Valine (Val), or a derivative or salt thereof. In some examples, the compound comprises AmPn-Arg-Val-DMA, AmPn-Ne- hydroxyarginine-Val-Ac, AmPn-Arg-Val-Ac, a derivative or salt thereof, or a combination thereof. , , derivatives or salts thereof, and combinations thereof. In some examples, the compound is selected from the group consisting of: , , , derivatives or salts thereof, and combinations thereof. In some examples, the compound is selected from the group consisting of: , , or salts thereof, and combinations thereof In some examples, the compound is selected from the group consisting of: , , es or salts thereof, and combinations thereof. In some examples, the compound is a salt. In some examples, the compound is a salt form of Formula I, Formula II, Formula III, Formula IV, Formula V, or a combination thereof with a counterion. In some examples, the compound is a salt form of Formula II with a counterion. In some examples, the compound is a salt form of Formula II with a counterion and the salt form of the compound is selected from the group consisting of: and combinations thereof. In some examples, the counterion is a monovalent or divalent counterion. In some examples, the counterion is selected from the group consisting of sodium, potassium, calcium, lithium, magnesium, manganese, ammonium, iron, and combinations thereof. In some examples, the compound is a potassium salt, sodium salt, calcium salt, iron salt, ammonium salt, or a combination thereof. In some examples, the compound comprises an agriculturally acceptable salt thereof and / or a pharmaceutically acceptable salt thereof. In some examples, the compound is a tetra-peptide. In some examples, the compound is an isolate of a marine organism, or a derivative or salt thereof. In some examples, the compound is a Salinispora isolate or a derivative or salt thereof. In some examples, the compound is a Salinispora pacifica isolate or a derivative or salt thereof. Also disclosed herein are compositions comprising any of the compounds disclosed herein. In some examples, the composition further comprises one or more agriculturally acceptable and / or pharmaceutically acceptable carriers. In some examples, the composition comprises a pharmaceutical composition, an agricultural composition, or a combination thereof. In some examples, the composition comprises a pesticide. In some examples, the composition comprises an herbicide. In some examples, the composition exhibits antimicrobial activity. In some examples, the composition results in at least 5 log reduction of a population of microbes. In some examples, the microbes are one or more microorganisms selected from the group consisting of gram negative bacteria. In some examples, the microbes are one or more microorganisms selected from the group consisting of Escherichia coli, Serratia marcescens, and Pantoea ananatis. In some examples, the composition further comprises a solvent, a carrier, an excipient, or a combination thereof. In some examples, the composition further comprises an agriculturally acceptable adjuvant or carrier. In some examples, the composition is formulated for delivery to a plant or animal. In some examples, the composition is formulated for delivery to a plant. In some examples, the plant comprises a crop. In some examples, the composition is formulated for delivery to onions. In some examples, the composition is formulated for delivery to an animal. In some examples, the animal is a companion animal, livestock, research animal, insect, or human. In some examples, the animal is an insect. In some examples, the insect is a bee, such as a honeybee. Also disclosed herein are nucleic acids encoding any of the compounds or compositions disclosed herein. Also disclosed herein are vectors encoding any of the nucleic acids disclosed herein. Also disclosed herein are cells comprising any of the vectors disclosed herein. Also disclosed herein are cells comprising any of the compounds or compositions disclosed herein. In some examples, the cell comprises a marine organism cell. In some examples, the cell comprises an actinobacterium cell. In some examples, the cell comprises a Salinispora cell. In some examples, the cell comprises a Salinispora pacifica cell. Also disclosed herein are methods of making any of the compounds disclosed herein. In some examples, the method is a biosynthetic method. In some examples, the method uses one or more enzymes derived from Salinispora, such as Salinispora pacifica. Also disclosed herein are methods of use of any of the compounds, compositions, nucleic acids, vectors, and / or cells disclosed herein. In some examples, the method comprises using the compound, composition, nucleic acid, vector, or cell as an antimicrobial, herbicide, pesticide, or combination thereof to control an undesirable population. In some examples, the method comprises using the compound, composition, nucleic acid, vector, or cell as a pesticide. In some examples, the method comprises using the compound, composition, nucleic acid, vector, or cell to control an undesirable population in plants. In some examples, the method comprises contacting the plants or the locus thereof with or applying to the soil or water the compound, composition, nucleic acid, vector, or cell. In some examples, the method further comprises applying an additional pesticide. In some examples, the undesirable population is an herbicide resistant or tolerant population, a pesticide resistant or tolerant population, an antimicrobial resistant or tolerant population, or a combination thereof. In some examples, the undesirable population comprises bacteria. Also disclosed herein are methods of reducing the activity of bacteria, the methods comprising exposing the bacteria to an effective amount any of the compounds, compositions, nucleic acids, vectors, and / or cells disclosed herein. Also disclosed herein are methods of reducing bacterial population, the methods comprising exposing the bacteria to an effective amount of any of the compounds, compositions, nucleic acids, vectors, and / or cells disclosed herein. Also disclosed herein are methods of killing bacteria, the methods comprising exposing the bacteria to an effective amount of any of the compounds, compositions, nucleic acids, vectors, and / or cells disclosed herein. Also disclosed herein are methods for treating, preventing, inhibiting, and / or ameliorating a disease or disorder in a plant or a subject in need thereof, the methods comprising administering to the plant or subject a therapeutically effective amount of any of the compounds, compositions, nucleic acids, vectors, and / or cells disclosed herein. In some examples, the disease or disorder comprises an infection, such as a microbial infection. Also disclosed herein are methods for treating, preventing, inhibiting, and / or ameliorating a microbial infection in a plant or a subject, comprising administering to the plant or subject an effective amount of any of the compounds, compositions, nucleic acids, vectors, and / or cells disclosed herein. In some examples, the microbial infection comprises a bacterial infection. In some examples, the bacteria comprise gram negative bacteria. In some examples, the bacteria comprise one or more bacteria selected from the group consisting of Escherichia coli, Serratia marcescens, and Pantoea ananatis. In some examples, the plant is a crop. In some examples, the plant is an onion. In some examples, the subject is an animal. In some examples, the animal is a companion animal, livestock, research animal, insect, or human. In some examples, the animal is an insect. In some examples, the insect is a bee, such as a honeybee. In some examples, the compound, composition, nucleic acid, and / or vector is delivered via cultured Salinispora pacifica. Also disclosed herein are methods of isolating and / or purifying a compound produced by a cell, wherein the compound comprises any of the compounds disclosed herein. In some examples, the cell comprises a marine organism cell. In some examples, the cell comprises an actinobacterium cell. In some examples, the cell comprises a Salinispora cell. In some examples, the cell comprises a Salinispora pacifica cell. Additional advantages of the disclosed compositions and methods will be set forth in part in the description which follows, and in part will be obvious from the description. The advantages of the disclosed compositions and methods will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the disclosed systems and methods, as claimed. The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims. BRIEF DESCRIPTION OF THE FIGURES The accompanying figures, which are incorporated in and constitute a part of this specification, illustrate several aspects of the disclosure, and together with the description, serve to explain the principles of the disclosure. Figure 1. Purification scheme of isolated phosphonates. Figure 2. Chemical structures of isolated phosphonates. Figure 3. Thioglycolate derivatization of compound 1 hydrolysate. Panel A – Extracted ion chromatogram of expected product (m / z 238.0830) in negative control containing 3- methylaspartate. Panel B – Extracted ion chromatogram of expected product in reaction containing compound 1 hydrolysate. Panel C – MS2spectrum of expected product with key fragments annotated. Figure 4. Synteny analysis of phosphonate biosynthetic gene clusters from Salinispora pacifica and Streptomyces monomycini. Figure 5. LC-HRMS data of compound 1. Top – extracted ion chromatogram for m / z 494.2123. Bottom – mass spectrum at 0.6 minutes. Figure 6. LC-HRMS-MS data of compound 1. Top – extracted ion chromatogram for m / z 494.2123. Bottom – mass spectrum at 0.75 minutes. Figure 7.1H NMR spectrum of compound 1 in D2O. Figure 8.1H NMR spectrum of compound 1 in DMSO-d6 with 0.05% trifluoroacetic acid (TFA). Figure 9.13C NMR spectrum of compound 1 in D2O. Figure 10.13C DEPT135 spectrum of compound 1 in D2O. Figure 11.1H-coupled31P spectrum of compound 1 in DMSO-d6 with 0.05% TFA. Figure 12.1H-31P HMBC spectrum of compound 1 in DMSO-d6with 0.05% TFA. Figure 13.1H-1H COSY spectrum of compound 1 in DMSO-d6with 0.05% TFA. Figure 14.1H-1H TOCSY spectrum of compound 1 in DMSO-d6 with 0.05% TFA. Figure 15.1H-13C HSQC spectrum of compound 1 in D2O. Figure 16.1H-13C HMBC spectrum of compound 1 in D2O. Figure 17.1H-15N HSQC spectrum of compound 1 in DMSO-d6 with 0.05% TFA. Figure 18.1H-15N HMBC spectrum of compound 1 in D2O. Figure 19. LC-HRMS of compound 2 (compound 2 / 3 mixture). Figure 20. LC-HRMS-MS of compound 2 (compound 2 / 3 mixture). Top – extracted ion chromatogram for m / z 425.1908. Bottom – mass spectrum at 0.6 minutes. Figure 21.1H NMR spectrum of compound 2 in D2O. Figure 22.13C NMR spectrum of compound 2 in D2O. Figure 23.13C DEPT 135 spectrum of compound 2 in D2O. Figure 24.1H-coupled31P spectrum of compound 2 in D2O. Figure 25.1H-31P HMBC spectrum of compound 2 in D2O. Figure 26.1H-1H COSY spectrum of compound 2 in D2O. Figure 27.1H-1H TOCSY spectrum of compound 2 in D2O. Figure 28.1H-13C HSQC spectrum of compound 2 in D2O. Figure 29.1H-13C HMBC spectrum of compound 2 in D2O. Figure 30.1H spectrum of compounds 2 and 3 in D2O. Resonances unique to compound 2 are indicated with *, while resonances unique to compound 3 are indicated with †. Remaining resonances overlap between compounds 2 and 3. Figure 31.1H spectrum of compounds 2 and 3 in DMSO-d6 with 0.05% TFA. Resonances unique to compound 2 are indicated with *, while resonances unique to compound 3 are indicated with †. Remaining resonances overlap between compounds 2 and 3. Figure 32.13C spectrum of compounds 2 and 3 in D2O. Resonances unique to compound 2 are indicated with *, while resonances unique to compound 3 are indicated with †. Remaining resonances overlap between compounds 2 and 3. Figure 33.13C DEPT 135 spectrum of compounds 2 and 3 in D2O. Figure 34.31P spectrum of compounds 2 and 3 in DMSO-d6 with 0.05% TFA Figure 35.1H-decoupled31P spectrum of compounds 2 and 3 in DMSO-d6with 0.05% TFA. Resonances unique to compound 2 are indicated with *, while resonances unique to compound 3 are indicated with †. Figure 36.1H-31P HMBC spectrum of compounds 2 and 3 in DMSO-d6 with 0.05% TFA Figure 37.1H-1H COSY spectrum of compounds 2 and 3 in D2O. Resonances unique to compound 2 are indicated with *, while resonances unique to compound 3 are indicated with †. Remaining resonances overlap between compounds 2 and 3. Figure 38.1H-1H COSY spectrum of compounds 2 and 3 in DMSO-d6 with 0.05% TFA. Resonances unique to compound 2 are indicated with *, while resonances unique to compound 3 are indicated with †. Remaining resonances overlap between compounds 2 and 3. Figure 39.1H-1H TOCSY spectrum of compounds 2 and 3 in D2O. Resonances unique to compound 2 are indicated with *, while resonances unique to compound 3 are indicated with †. Remaining resonances overlap between compounds 2 and 3. Figure 40.1H-1H TOCSY spectrum of compounds 2 and 3 in DMSO-d6 with 0.05% TFA. Resonances unique to compound 2 are indicated with *, while resonances unique to compound 3 are indicated with †. Remaining resonances overlap between compounds 2 and 3. Figure 41.1H-13C HSQC spectrum of compounds 2 and 3 in D2O. Figure 42.1H-13C HMBC spectrum of compounds 2 and 3 in D2O. Resonances unique to compound 2 are indicated with *, while resonances unique to compound 3 are indicated with †. Remaining resonances overlap between compounds 2 and 3. Figure 43.1H-15N HSQC spectrum of compounds 2 and 3 in DMSO-d6 with 0.05% TFA. Resonances unique to compound 3 are indicated with †. Remaining resonances overlap between compounds 2 and 3. Figure 44.1H-15N HMBC spectrum of compounds 2 and 3 in DMSO-d6 with 0.05% TFA. Figure 45. LC-HRMS-MS data of pure compound 3. Figure 46. LC-HRMS-MS data of compound 3. Top – extracted ion chromatogram for m / z 409.1959. Bottom – mass spectrum at 5.75 minutes. Figure 47.1H NMR spectrum of compound 3 in D2O. Figure 48.1H-31P HMBC spectrum of compound 3 in D2O. Figure 49.1H-1H COSY spectrum of compound 3 in D2O. Figure 50.1H-1H TOCSY spectrum of compound 3 in D2O. Figure 51.1H-13C HMBC spectrum of compound 3 in D2O. Figure 52. LC-HRMS data of purified aminomethylphosphonate. Figure 53.1H NMR spectrum of purified aminomethylphosphonate in 90% H2O / 10% D2O. Figure 54.31P NMR spectrum of purified aminomethylphosphonate in 90% H2O / 10% D2O. Figure 55.1H-31P HMBC spectrum of purified aminomethylphosphonate in 90% H2O / 10% D2O. Figure 56.1H NMR spectrum of partially purified 2-aminoethylphosphonate in 90% H2O / 10% D2O. Figure 57.31P NMR spectrum of partially purified 2-aminoethylphosphonate in 90% H2O / 10% D2O. Figure 58.1H-31P HMBC spectrum of partially purified 2-aminoethylphosphonate in 90% H2O / 10% D2O. Figure 59. Marfey’s analysis for absolution configuration of arginine in compound 1. Extracted ion chromatograms for FDAA derivatized arginine (m / z 427.1684). Figure 60. Marfey’s analysis for absolution configuration of valine in compound 1. Extracted ion chromatograms for FDAA derivatized valine (m / z 370.1357). Figure 61. Marfey’s analysis for absolution configuration of arginine in compound 2. Extracted ion chromatograms for FDAA derivatized arginine (m / z 427.1684). Figure 62. Marfey’s analysis for absolution configuration of valine in compound 2. Extracted ion chromatograms for FDAA derivatized valine (m / z 370.1357). Figure 63. Comparison of arginine stereochemistry in argolaphos and compound 2 by Marfey’s analysis. Extracted ion chromatograms for FDAA derivatized arginine (m / z 427.1684). Figure 64. Comparison of valine stereochemistry in argolaphos and compound 2 by Marfey’s analysis. Extracted ion chromatograms for FDAA derivatized valine (m / z 370.1357). Figure 65. LC-HRMS analysis of extract from S. albus pAE4. (top) EIC of Compound 1; (middle) EIC of Compound 2; (bottom) EIC of Compound 3. Figure 66. LC-HRMS analysis of extract from S. albus pKSJ452. (top) EIC of Compound 1; (middle) EIC of Compound 2; (bottom) EIC of Compound 3. Figure 67. LC-HRMS analysis of TCEP treated extracts from S. albus pAE4 and S. albus pKSJ452. Figure 68. LC-HRMS-MS analysis of TCEP treated extract from S. albus pKSJ452 (MS at 6.1 min). Figure 69. LC-HRMS analysis of TCEP treated compound 1 hydrolysate. Figure 70. LC-HRMS analysis of thioglycolate treated extract from S. albus pAE4 and S. albus pKSJ452. Figure 71. LC-HRMS-MS analysis of thioglycolate treated extract from S. albus pKSJ452 (MS at 6.1 min). Figure 72. LC-HRMS analysis of thioglycolate treated 3-methylaspartate and compound 1 hydrolysate. Figure 73. LC-HRMS-MS analysis of thioglycolate treated compound 1 hydrolysate (MS at 4.7 min). DETAILED DESCRIPTION The compositions, methods, and systems described herein may be understood more readily by reference to the following detailed description of specific aspects of the disclosed subject matter and the Examples included therein. Before the present compositions, methods, and systems are disclosed and described, it is to be understood that the aspects described below are not limited to specific synthetic methods or specific reagents, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only and is not intended to be limiting. Also, throughout this specification, various publications are referenced. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which the disclosed matter pertains. The references disclosed are also individually and specifically incorporated by reference herein for the material contained in them that is discussed in the sentence in which the reference is relied upon. General Definitions In this specification and in the claims that follow, reference will be made to a number of terms, which shall be defined to have the following meanings. Throughout the description and claims of this specification, the word “comprise” and other forms of the word, such as “comprising” and “comprises,” means including but not limited to, and is not intended to exclude, for example, other additives, components, integers, or steps. As used in the description and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a composition” includes mixtures of two or more such compositions, reference to “an agent” includes mixtures of two or more such agents, reference to “the component” includes mixtures of two or more such components, and the like. “Optional” or “optionally” means that the subsequently described event or circumstance can or cannot occur, and that the description includes instances where the event or circumstance occurs and instances where it does not. Ranges can be expressed herein as from “about” one particular value, and / or to “about” another particular value. By “about” is meant within 5% of the value, e.g., within 4, 3, 2, or 1% of the value. When such a range is expressed, another aspect includes from the one particular value and / or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another aspect. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint. Values can be expressed herein as an “average” value. “Average” generally refers to the statistical mean value. By “substantially” is meant within 5%, e.g., within 4%, 3%, 2%, or 1%. “Exemplary” means “an example of” and is not intended to convey an indication of a preferred or ideal embodiment. “Such as” is not used in a restrictive sense, but for explanatory purposes. It is understood that throughout this specification the identifiers “first” and “second” are used solely to aid in distinguishing the various components and steps of the disclosed subject matter. The identifiers “first” and “second” are not intended to imply any particular order, amount, preference, or importance to the components or steps modified by these terms. References in the specification and concluding claims to parts by weight of a particular element or component in a composition denotes the weight relationship between the element or component and any other elements or components in the composition or article for which a part by weight is expressed. Thus, in a compound containing 2 parts by weight of component X and 5 parts by weight component Y, X and Y are present at a weight ratio of 2:5, and are present in such ratio regardless of whether additional components are contained in the compound. A weight percent (wt. %) of a component, unless specifically stated to the contrary, is based on the total weight of the formulation or composition in which the component is included. The term “or combinations thereof” as used herein refers to all permutations and combinations of the listed items preceding the term. For example, “A, B, C, or combinations thereof” is intended to include at least one of: A, B, C, AB, AC, BC, or ABC, and if order is important in a particular context, also BA, CA, CB, CBA, BCA, ACB, BAC, or CAB. Continuing with this example, expressly included are combinations that contain repeats of one or more item or term, such as BB, AAA, AB, BBC, AAABCCCC, CBBAAA, CABABB, and so forth. The skilled artisan will understand that typically there is no limit on the number of items or terms in any combination, unless otherwise apparent from the context. As used herein, Me refers to a methyl group; OMe refers to a methoxy group; and i-Pr refers to an isopropyl group. As used herein, agriculturally acceptable salts and esters refer to salts and esters that exhibit herbicidal activity, or that are or can be converted in plants, water, or soil to the referenced herbicide. Exemplary agriculturally acceptable esters are those that are or can be hydrolyzed, oxidized, metabolized, or otherwise converted, e.g., in plants, water, or soil, to the corresponding carboxylic acid which, depending on the pH, may be in the dissociated or undissociated form. As used herein, by a “subject” is meant an individual. Thus, the “subject” can include domesticated animals (e.g., cats, dogs, etc.), livestock (e.g., cattle, horses, pigs, sheep, goats, etc.), laboratory animals (e.g., mouse, rabbit, rat, guinea pig, etc.), birds, and insects. “Subject” can also include a mammal, such as a primate or a human. Thus, the subject can be a human or veterinary patient. The term “patient” refers to a subject under the treatment of a clinician, e.g., physician. As used herein, antimicrobials include, for example, antibacterials, antifungals, and antivirals. As used herein, “antimicrobial” refers to the ability to treat or control (e.g., reduce, prevent, treat, or eliminate) the growth of a microbe at any concentration. Similarly, the terms “antibacterial,” “antifungal,” and “antiviral” refer to the ability to treat or control the growth of bacteria, fungi, and viruses at any concentration, respectively. The term “inhibit” refers to a decrease in an activity, response, condition, disease, or other biological parameter. This can include but is not limited to the complete ablation of the activity, response, condition, or disease. This can also include, for example, a 10% reduction in the activity, response, condition, or disease as compared to the native or control level. Thus, the reduction can be a 10, 20, 30, 40, 50, 60, 70, 80, 90, 100%, or any amount of reduction in between as compared to native or control levels. As used herein, “reduce” or other forms of the word, such as “reducing” or “reduction,” refers to lowering of an event or characteristic (e.g., microbe population / infection). It is understood that the reduction is typically in relation to some standard or expected value, in other words it is relative, but that it is not always necessary for the standard or relative value to be referred to. For example, “reducing microbial infection” means reducing the spread of a microbial infection relative to a standard or a control. As used herein, “prevent” or other forms of the word, such as “preventing” or “prevention,” refers to stopping a particular event or characteristic, stabilizing or delaying the development or progression of a particular event or characteristic, or minimizing the chances that a particular event or characteristic will occur. “Prevent” does not require comparison to a control as it is typically more absolute than, for example, “reduce.” As used herein, something could be reduced but not prevented, but something that is reduced could also be prevented. Likewise, something could be prevented but not reduced, but something that is prevented could also be reduced. It is understood that where reduce or prevent are used, unless specifically indicated otherwise, the use of the other word is also expressly disclosed. For example, the terms “prevent” or “suppress” can refer to a treatment that forestalls or slows the onset of a disease or condition or reduced the severity of the disease or condition. Thus, if a treatment can treat a disease in a subject having symptoms of the disease, it can also prevent or suppress that disease in a subject who has yet to suffer some or all of the symptoms. As used herein, “treat” or other forms of the word, such as “treated” or “treatment,” refers to administration of a composition or performing a method in order to reduce, prevent, inhibit, or eliminate a particular characteristic or event (e.g., microbe growth or survival). The term “control” is used synonymously with the term “treat.” The term “treatment” refers to the medical management of a patient with the intent to cure, ameliorate, stabilize, or prevent a disease, pathological condition, or disorder. This term includes active treatment, that is, treatment directed specifically toward the improvement of a disease, pathological condition, or disorder, and also includes causal treatment, that is, treatment directed toward removal of the cause of the associated disease, pathological condition, or disorder. In addition, this term includes palliative treatment, that is, treatment designed for the relief of symptoms rather than the curing of the disease, pathological condition, or disorder; preventative treatment, that is, treatment directed to minimizing or partially or completely inhibiting the development of the associated disease, pathological condition, or disorder; and supportive treatment, that is, treatment employed to supplement another specific therapy directed toward the improvement of the associated disease, pathological condition, or disorder. By way of example, in the context of microbial infections, “treating,” “treat,” and “treatment” as used herein, refers to partially or completely inhibiting or reducing the microbial infections which the subject is suffering. In one embodiment, this term refers to an action that occurs while a patient is suffering from, or is diagnosed with, the microbial infections, which reduces the severity of the condition, or retards or slows the progression of the condition. Treatment need not result in a complete cure of the condition; partial inhibition or reduction of the microbial infections is encompassed by this term. The term “therapeutically effective amount” refers to the amount of the composition used is of sufficient quantity to ameliorate one or more causes or symptoms of a disease or disorder. Such amelioration only requires a reduction or alteration, not necessarily elimination. The term “pharmaceutically acceptable” refers to those compounds, materials, compositions, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problems or complications commensurate with a reasonable benefit / risk ratio. As used herein, “molecular weight” refers to number average molecular weight as measured by1H NMR spectroscopy, unless indicated otherwise. As used herein, the term “delivery” encompasses both local and systemic delivery. For example, delivery of mRNA encompasses situations in which an mRNA is delivered to a target tissue and the encoded protein or peptide is expressed and retained within the target tissue (also referred to as “local distribution” or “local delivery”), and situations in which an mRNA is delivered to a target tissue and the encoded protein or peptide is expressed and secreted into patient's circulation system (e.g., serum) and systematically distributed and taken up by other tissues (also referred to as “systemic distribution” or “systemic delivery). As used herein, the term “encapsulation,” or grammatical equivalent, refers to the process of confining an individual nucleic acid molecule within a nanoparticle. As used herein, “expression” of a mRNA refers to translation of an mRNA into a peptide (e.g., an antigen), polypeptide, or protein (e.g., an enzyme) and also can include, as indicated by context, the post-translational modification of the peptide, polypeptide or fully assembled protein (e.g., enzyme). In this application, the terms “expression” and “production,” and grammatical equivalent, are used inter-changeably. As used herein, the term “messenger RNA (mRNA)” refers to a polynucleotide that encodes at least one peptide, polypeptide or protein. mRNA as used herein encompasses both modified and unmodified RNA. mRNA may contain one or more coding and non-coding regions. mRNA can be purified from natural sources, produced using recombinant expression systems and optionally purified, chemically synthesized, etc. Where appropriate, e.g., in the case of chemically synthesized molecules, mRNA can comprise nucleoside analogs such as analogs having chemically modified bases or sugars, backbone modifications, etc. An mRNA sequence is presented in the 5′ to 3′ direction unless otherwise indicated. In some embodiments, an mRNA is or comprises natural nucleosides (e.g., adenosine, guanosine, cytidine, uridine); nucleoside analogs (e.g., 2-aminoadenosine, 2-thiothymidine, inosine, pyrrolo-pyrimidine, 3-methyl adenosine, 5-methylcytidine, C-5 propynyl-cytidine, C-5 propynyl-uridine, 2-aminoadenosine, C5-bromouridine, C5-fluorouridine, C5-iodouridine, C5-propynyl-uridine, C5-propynyl- cytidine, C5-methylcytidine, 2-aminoadenosine, 7-deazaadenosine, 7-deazaguanosine, 8- oxoadenosine, 8-oxoguanosine, O(6)-methylguanine, 2-thiocytidine, pseudouridine, and 5- methylcytidine); chemically modified bases; biologically modified bases (e.g., methylated bases); intercalated bases; modified sugars (e.g., 2′-fluororibose, ribose, 2′-deoxyribose, arabinose, and hexose); and / or modified phosphate groups (e.g., phosphorothioates and 5′-N- phosphoramidite linkages). As used herein, the term “nucleic acid,” in its broadest sense, refers to any compound and / or substance that is or can be incorporated into a polynucleotide chain. In some embodiments, a nucleic acid is a compound and / or substance that is or can be incorporated into a polynucleotide chain via a phosphodiester linkage. In some embodiments, “nucleic acid” refers to individual nucleic acid residues (e.g., nucleotides and / or nucleosides). In some embodiments, “nucleic acid” refers to a polynucleotide chain comprising individual nucleic acid residues. In some embodiments, “nucleic acid” encompasses RNA as well as single and / or double-stranded DNA and / or cDNA. Furthermore, the terms “nucleic acid,” “DNA,” “RNA,” and / or similar terms include nucleic acid analogs, i.e., analogs having other than a phosphodiester backbone. In some examples, the term “nucleic acid” as used herein means natural and synthetic DNA, RNA, oligonucleotides, oligonucleosides, and derivatives thereof. For ease of discussion, such nucleic acids are at times collectively referred to herein as “constructs,” “plasmids,” or “vectors.” The term “gene” as used in this specification refers to a segment of deoxyribonucleotides (DNA) possessing the information required for synthesis of a functional biological product such as a protein or ribonucleic acid (RNA). The term “genetic engineering” is used to indicate various methods involved in gene manipulation including isolation, joining, introducing of gene(s) as well as methods to isolate select organisms containing the manipulated gene(s). As specified herein, the term “DNA construct” refers to a sequence of deoxyribonucleotides including deoxyribonucleotides obtained from one or more sources. The term “gene expression” refers to efficient transcription and translation of genetic information contained in concerned genes. The term “recombinant” cells or population of cells refers to cells or population of cells into which an exogenous nucleic acid sequence is introduced using a delivery vehicle such as a plasmid. Chemical Definitions Unless otherwise defined, 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. The organic moieties mentioned when defining variable positions within the general formulae described herein (e.g., the term “halogen”) are collective terms for the individual substituents encompassed by the organic moiety. The prefix Cn-Cmpreceding a group or moiety indicates, in each case, the possible number of carbon atoms in the group or moiety that follows. The term “ion,” as used herein, refers to any molecule, portion of a molecule, cluster of molecules, molecular complex, moiety, or atom that contains a charge (positive, negative, or both at the same time within one molecule, cluster of molecules, molecular complex, or moiety (e.g., zwitterions)) or that can be made to contain a charge. Methods for producing a charge in a molecule, portion of a molecule, cluster of molecules, molecular complex, moiety, or atom are disclosed herein and can be accomplished by methods known in the art, e.g., protonation, deprotonation, oxidation, reduction, alkylation, acetylation, esterification, de-esterification, hydrolysis, etc. The term “anion” is a type of ion and is included within the meaning of the term “ion.” An “anion” is any molecule, portion of a molecule (e.g., zwitterion), cluster of molecules, molecular complex, moiety, or atom that contains a net negative charge or that can be made to contain a net negative charge. The term “anion precursor” is used herein to specifically refer to a molecule that can be converted to an anion via a chemical reaction (e.g., deprotonation). The term “cation” is a type of ion and is included within the meaning of the term “ion.” A “cation” is any molecule, portion of a molecule (e.g., zwitterion), cluster of molecules, molecular complex, moiety, or atom, that contains a net positive charge or that can be made to contain a net positive charge. The term “cation precursor” is used herein to specifically refer to a molecule that can be converted to a cation via a chemical reaction (e.g., protonation or alkylation). As used herein, the term “substituted” is contemplated to include all permissible substituents of organic compounds. In a broad aspect, the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, and aromatic and nonaromatic substituents of organic compounds. Illustrative substituents include, for example, those described below. The permissible substituents can be one or more and the same or different for appropriate organic compounds. For purposes of this disclosure, the heteroatoms, such as nitrogen, can have hydrogen substituents and / or any permissible substituents of organic compounds described herein which satisfy the valencies of the heteroatoms. This disclosure is not intended to be limited in any manner by the permissible substituents of organic compounds. Also, the terms “substitution” or “substituted with” include the implicit proviso that such substitution is in accordance with permitted valence of the substituted atom and the substituent, and that the substitution results in a stable compound, e.g., a compound that does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, etc. “Z1,” “Z2,” “Z3,” and “Z4” are used herein as generic symbols to represent various specific substituents. These symbols can be any substituent, not limited to those disclosed herein, and when they are defined to be certain substituents in one instance, they can, in another instance, be defined as some other substituents. The term “aliphatic” as used herein refers to a non-aromatic hydrocarbon group and includes branched and unbranched, alkyl, alkenyl, or alkynyl groups. As used herein, the term “alkyl” refers to saturated, straight-chained or branched saturated hydrocarbon moieties. Unless otherwise specified, C1-C24(e.g., C1-C22, C1-C20, C1-C18, C1-C16, C1-C14, C1-C12, C1-C10, C1-C8, C1-C6, or C1-C4) alkyl groups are intended. Examples of alkyl groups include methyl, ethyl, propyl, 1-methyl-ethyl, butyl, 1-methyl-propyl, 2-methyl- propyl, 1,1-dimethyl-ethyl, pentyl, 1-methyl-butyl, 2-methyl-butyl, 3-methyl-butyl, 2,2- dimethyl-propyl, 1-ethyl-propyl, hexyl, 1,1-dimethyl-propyl, 1,2-dimethyl-propyl, 1-methyl- pentyl, 2-methyl-pentyl, 3-methyl-pentyl, 4-methyl-pentyl, 1,1-dimethyl-butyl, 1,2-dimethyl- butyl, 1,3-dimethyl-butyl, 2,2-dimethyl-butyl, 2,3-dimethyl-butyl, 3,3-dimethyl-butyl, 1-ethyl- butyl, 2-ethyl-butyl, 1,1,2-trimethyl-propyl, 1,2,2-trimethyl-propyl, 1-ethyl-1-methyl-propyl, 1- ethyl-2-methyl-propyl, heptyl, octyl, nonyl, decyl, dodecyl, tetradecyl, hexadecyl, eicosyl, tetracosyl, and the like. Alkyl substituents may be unsubstituted or substituted with one or more chemical moieties. The alkyl group can be substituted with one or more groups including, but not limited to, hydroxyl, halogen, acyl, alkyl, alkoxy, alkenyl, alkynyl, aryl, heteroaryl, aldehyde, amino, cyano, carboxylic acid, ester, ether, ketone, nitro, phosphonyl, silyl, sulfo-oxo, sulfonyl, sulfone, sulfoxide, or thiol, as described below, provided that the substituents are sterically compatible and the rules of chemical bonding and strain energy are satisfied. Throughout the specification “alkyl” is generally used to refer to both unsubstituted alkyl groups and substituted alkyl groups; however, substituted alkyl groups are also specifically referred to herein by identifying the specific substituent(s) on the alkyl group. For example, the term “halogenated alkyl” specifically refers to an alkyl group that is substituted with one or more halides (halogens; e.g., fluorine, chlorine, bromine, or iodine). The term “alkoxyalkyl” specifically refers to an alkyl group that is substituted with one or more alkoxy groups, as described below. The term “alkylamino” specifically refers to an alkyl group that is substituted with one or more amino groups, as described below, and the like. When “alkyl” is used in one instance and a specific term such as “alkylalcohol” is used in another, it is not meant to imply that the term “alkyl” does not also refer to specific terms such as “alkylalcohol” and the like. This practice is also used for other groups described herein. That is, while a term such as “cycloalkyl” refers to both unsubstituted and substituted cycloalkyl moieties, the substituted moieties can, in addition, be specifically identified herein; for example, a particular substituted cycloalkyl can be referred to as, e.g., an “alkylcycloalkyl.” Similarly, a substituted alkoxy can be specifically referred to as, e.g., a “halogenated alkoxy,” a particular substituted alkenyl can be, e.g., an “alkenylalcohol,” and the like. Again, the practice of using a general term, such as “cycloalkyl,” and a specific term, such as “alkylcycloalkyl,” is not meant to imply that the general term does not also include the specific term. As used herein, the term “alkenyl” refers to unsaturated, straight-chained, or branched hydrocarbon moieties containing a double bond. Unless otherwise specified, C2-C24(e.g., C2-C22, C2-C20, C2-C18, C2-C16, C2-C14, C2-C12, C2-C10, C2-C8, C2-C6, or C2-C4) alkenyl groups are intended. Alkenyl groups may contain more than one unsaturated bond. Examples include ethenyl, 1-propenyl, 2-propenyl, 1-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1- propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 1-pentenyl, 2- pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl, 3-methyl-1-butenyl, 1-methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3- butenyl, 3-methyl-3-butenyl, 1,1-dimethyl-2-propenyl, 1,2-dimethyl-1-propenyl, 1,2-dimethyl-2- propenyl, 1-ethyl-1-propenyl, 1-ethyl-2-propenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-1-pentenyl, 2-methyl-1-pentenyl, 3-methyl-1-pentenyl, 4-methyl-1- pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl, 1-methyl-3-pentenyl, 2-methyl-3-pentenyl, 3-methyl-3-pentenyl, 4-methyl-3-pentenyl, 1-methyl- 4-pentenyl, 2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl, 1,1-dimethyl-2- butenyl, 1,1-dimethyl-3-butenyl, 1,2-dimethyl-1-butenyl, 1,2-dimethyl-2-butenyl, 1,2-dimethyl- 3-butenyl, 1,3-dimethyl-1-butenyl, 1,3-dimethyl-2-butenyl, 1,3-dimethyl-3-butenyl, 2,2- dimethyl-3-butenyl, 2,3-dimethyl-1-butenyl, 2,3-dimethyl-2-butenyl, 2,3-dimethyl-3-butenyl, 3,3-dimethyl-1-butenyl, 3,3-dimethyl-2-butenyl, 1-ethyl-1-butenyl, 1-ethyl-2-butenyl, 1-ethyl-3- butenyl, 2-ethyl-1-butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl, 1,1,2-trimethyl-2-propenyl, 1- ethyl-1-methyl-2-propenyl, 1-ethyl-2-methyl-1-propenyl, and 1-ethyl-2-methyl-2-propenyl. The term “vinyl” refers to a group having the structure –CH=CH2; 1-propenyl refers to a group with the structure –CH=CH-CH3; and 2-propenyl refers to a group with the structure –CH2-CH=CH2. Asymmetric structures such as (Z1Z2)C=C(Z3Z4) are intended to include both the E and Z isomers. This can be presumed in structural formulae herein wherein an asymmetric alkene is present, or it can be explicitly indicated by the bond symbol C=C. Alkenyl substituents may be unsubstituted or substituted with one or more chemical moieties. Examples of suitable substituents include, for example, alkyl, alkoxy, alkenyl, alkynyl, aryl, heteroaryl, acyl, aldehyde, amino, cyano, carboxylic acid, ester, ether, halide, hydroxyl, ketone, nitro, phosphonyl, silyl, sulfo-oxo, sulfonyl, sulfone, sulfoxide, or thiol, as described below, provided that the substituents are sterically compatible and the rules of chemical bonding and strain energy are satisfied. As used herein, the term “alkynyl” represents straight-chained or branched hydrocarbon moieties containing a triple bond. Unless otherwise specified, C2-C24(e.g., C2-C24, C2-C20, C2- C18, C2-C16, C2-C14, C2-C12, C2-C10, C2-C8, C2-C6, or C2-C4) alkynyl groups are intended. Alkynyl groups may contain more than one unsaturated bond. Examples include C2-C6-alkynyl, such as ethynyl, 1-propynyl, 2-propynyl (or propargyl), 1-butynyl, 2-butynyl, 3-butynyl, 1- methyl-2-propynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 3-methyl-1-butynyl, 1- methyl-2-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 1,1-dimethyl-2-propynyl, 1-ethyl-2- propynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 3-methyl-1-pentynyl, 4- methyl-1-pentynyl, 1-methyl-2-pentynyl, 4-methyl-2-pentynyl, 1-methyl-3-pentynyl, 2-methyl- 3-pentynyl, 1-methyl-4-pentynyl, 2-methyl-4-pentynyl, 3-methyl-4-pentynyl, 1,1-dimethyl-2- butynyl, 1,1-dimethyl-3-butynyl, 1,2-dimethyl-3-butynyl, 2,2-dimethyl-3-butynyl, 3,3-dimethyl- 1-butynyl, 1-ethyl-2-butynyl, 1-ethyl-3-butynyl, 2-ethyl-3-butynyl, and 1-ethyl-1-methyl-2- propynyl. Alkynyl substituents may be unsubstituted or substituted with one or more chemical moieties. Examples of suitable substituents include, for example, alkyl, alkoxy, alkenyl, alkynyl, aryl, heteroaryl, acyl, aldehyde, amino, cyano, carboxylic acid, ester, ether, halide, hydroxyl, ketone, nitro, phosphonyl, silyl, sulfo-oxo, sulfonyl, sulfone, sulfoxide, or thiol, as described below. As used herein, the term “aryl,” as well as derivative terms such as aryloxy, refers to groups that include a monovalent aromatic carbocyclic group of from 3 to 50 carbon atoms. Aryl groups can include a single ring or multiple condensed rings. In some examples, aryl groups include C6-C10 aryl groups. Examples of aryl groups include, but are not limited to, benzene, phenyl, biphenyl, naphthyl, tetrahydronaphthyl, phenylcyclopropyl, phenoxybenzene, and indanyl. The term “aryl” also includes “heteroaryl,” which is defined as a group that contains an aromatic group that has at least one heteroatom incorporated within the ring of the aromatic group. Examples of heteroatoms include, but are not limited to, nitrogen, oxygen, sulfur, and phosphorus. The term “non-heteroaryl,” which is also included in the term “aryl,” defines a group that contains an aromatic group that does not contain a heteroatom. The aryl substituents may be unsubstituted or substituted with one or more chemical moieties. Examples of suitable substituents include, for example, alkyl, alkoxy, alkenyl, alkynyl, aryl, heteroaryl, acyl, aldehyde, amino, cyano, carboxylic acid, ester, ether, halide, hydroxyl, ketone, nitro, phosphonyl, silyl, sulfo-oxo, sulfonyl, sulfone, sulfoxide, or thiol as described herein. The term “biaryl” is a specific type of aryl group and is included in the definition of aryl. Biaryl refers to two aryl groups that are bound together via a fused ring structure, as in naphthalene, or are attached via one or more carbon-carbon bonds, as in biphenyl. The term “cycloalkyl” as used herein is a non-aromatic carbon-based ring composed of at least three carbon atoms. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc. The term “heterocycloalkyl” is a cycloalkyl group as defined above where at least one of the carbon atoms of the ring is substituted with a heteroatom such as, but not limited to, nitrogen, oxygen, sulfur, or phosphorus. The cycloalkyl group and heterocycloalkyl group can be substituted or unsubstituted. The cycloalkyl group and heterocycloalkyl group can be substituted with one or more groups including, but not limited to, alkyl, alkoxy, alkenyl, alkynyl, aryl, heteroaryl, acyl, aldehyde, amino, cyano, carboxylic acid, ester, ether, halide, hydroxyl, ketone, nitro, phosphonyl, silyl, sulfo-oxo, sulfonyl, sulfone, sulfoxide, or thiol as described herein. The term “cycloalkenyl” as used herein is a non-aromatic carbon-based ring composed of at least three carbon atoms and containing at least one double bound, i.e., C=C. Examples of cycloalkenyl groups include, but are not limited to, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclopentadienyl, cyclohexenyl, cyclohexadienyl, and the like. The term “heterocycloalkenyl” is a type of cycloalkenyl group as defined above and is included within the meaning of the term “cycloalkenyl,” where at least one of the carbon atoms of the ring is substituted with a heteroatom such as, but not limited to, nitrogen, oxygen, sulfur, or phosphorus. The cycloalkenyl group and heterocycloalkenyl group can be substituted or unsubstituted. The cycloalkenyl group and heterocycloalkenyl group can be substituted with one or more groups including, but not limited to, alkyl, alkoxy, alkenyl, alkynyl, aryl, heteroaryl, acyl, aldehyde, amino, cyano, carboxylic acid, ester, ether, halide, hydroxyl, ketone, nitro, phosphonyl, silyl, sulfo-oxo, sulfonyl, sulfone, sulfoxide, or thiol as described herein. The term “cyclic group” is used herein to refer to either aryl groups, non-aryl groups (i.e., cycloalkyl, heterocycloalkyl, cycloalkenyl, and heterocycloalkenyl groups), or both. Cyclic groups have one or more ring systems (e.g., monocyclic, bicyclic, tricyclic, polycyclic, etc.) that can be substituted or unsubstituted. A cyclic group can contain one or more aryl groups, one or more non-aryl groups, or one or more aryl groups and one or more non-aryl groups. The term “acyl” as used herein is represented by the formula –C(O)Z1where Z1can be a hydrogen, hydroxyl, alkoxy, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl group described above. As used herein, the term “acyl” can be used interchangeably with “carbonyl.” Throughout this specification “C(O)” or “CO” is a shorthand notation for C=O. The term “acetal” as used herein is represented by the formula (Z1Z2)C(=OZ3)(=OZ4), where Z1, Z2, Z3, and Z4can be, independently, a hydrogen, halogen, hydroxyl, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl group described above. The term “alkanol” as used herein is represented by the formula Z1OH, where Z1can be an alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl group described above. As used herein, the term “alkoxy” as used herein is an alkyl group bound through a single, terminal ether linkage; that is, an “alkoxy” group can be defined as to a group of the formula , where Z1is unsubstituted or substituted alkyl as defined above. Unless otherwise specified, alkoxy groups wherein Z1is a C1-C24(e.g., C1-C22, C1-C20, C1-C18, C1-C16, C1-C14, C1- C12, C1-C10, C1-C8, C1-C6, or C1-C4) alkyl group are intended. Examples include methoxy, ethoxy, propoxy, 1-methyl-ethoxy, butoxy, 1-methyl-propoxy, 2-methyl-propoxy, 1,1-dimethyl- ethoxy, pentoxy, 1-methyl-butyloxy, 2-methyl-butoxy, 3-methyl-butoxy, 2,2-di-methyl-propoxy, 1-ethyl-propoxy, hexoxy, 1,1-dimethyl-propoxy, 1,2-dimethyl-propoxy, 1-methyl-pentoxy, 2- methyl-pentoxy, 3-methyl-pentoxy, 4-methyl-penoxy, 1,1-dimethyl-butoxy, 1,2-dimethyl- butoxy, 1,3-dimethyl-butoxy, 2,2-dimethyl-butoxy, 2,3-dimethyl-butoxy, 3,3-dimethyl-butoxy, 1-ethyl-butoxy, 2-ethylbutoxy, 1,1,2-trimethyl-propoxy, 1,2,2-trimethyl-propoxy, 1-ethyl-1- methyl-propoxy, and 1-ethyl-2-methyl-propoxy. The term “aldehyde” as used herein is represented by the formula —C(O)H. Throughout this specification “C(O)” is a shorthand notation for C=O. The term “amino” as used herein are represented by the formula —NZ1Z2Z3, where Z1, Z2, and Z3can each be substitution group as described herein, such as hydrogen, an alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl group described above. The terms “amide” or “amido” as used herein are represented by the formula — C(O)NZ1Z2, where Z1and Z2can each be substitution group as described herein, such as hydrogen, an alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl group described above. The term “anhydride” as used herein is represented by the formula Z1C(O)OC(O)Z2where Z1and Z2, independently, can be an alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl group described above. The term “cyclic anhydride” as used herein is represented by the formula: where Z1can be an alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl group described above. The term “azide” as used herein is represented by the formula –N=N=N. The term “carboxylic acid” as used herein is represented by the formula —C(O)OH. A “carboxylate” or “carboxyl” group as used herein is represented by the formula—C(O)O-.The term “cyano” as used herein is represented by the formula —CN. The term “ester” as used herein is represented by the formula —OC(O)Z1or —C(O)OZ1, where Z1can be an alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl group described above. The term “ether” as used herein is represented by the formula Z1OZ2, where Z1and Z2can be, independently, an alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl group described above. The term “epoxy” or “epoxide” as used herein refers to a cyclic ether with a three atom ring and can represented by the formula: where Z1, Z2, Z3, and Z4can be, independently, an alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl group described above The term “ketone” as used herein is represented by the formula Z1C(O)Z2, where Z1and Z2can be, independently, an alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl group described above. The term “halide” or “halogen” or “halo” as used herein refers to fluorine, chlorine, bromine, and iodine. The term “hydroxyl” as used herein is represented by the formula —OH. The term “nitro” as used herein is represented by the formula —NO2. The term “phosphonyl” is used herein to refer to the phospho-oxo group represented by the formula —P(O)(OZ1)2, where Z1can be hydrogen, an alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl group described above. The term “silyl” as used herein is represented by the formula —SiZ1Z2Z3, where Z1, Z2, and Z3can be, independently, hydrogen, alkyl, alkoxy, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl group described above. The term “sulfonyl” or “sulfone” is used herein to refer to the sulfo-oxo group represented by the formula —S(O)2Z1, where Z1can be hydrogen, an alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl group described above. The term “sulfide” as used herein comprises the formula —S—. The term “thiol” as used herein is represented by the formula —SH. “R1,” “R2,” “R3,” “Rn,” etc., where n is some integer, as used herein can, independently, possess one or more of the groups listed above. For example, if R1is a straight chain alkyl group, one of the hydrogen atoms of the alkyl group can optionally be substituted with a hydroxyl group, an alkoxy group, an amino group, an alkyl group, a halide, and the like. Depending upon the groups that are selected, a first group can be incorporated within a second group or, alternatively, the first group can be pendant (i.e., attached) to the second group. For example, with the phrase “an alkyl group comprising an amino group,” the amino group can be incorporated within the backbone of the alkyl group. Alternatively, the amino group can be attached to the backbone of the alkyl group. The nature of the group(s) that is (are) selected will determine if the first group is embedded or attached to the second group. Unless stated to the contrary, a formula with chemical bonds shown only as solid lines and not as wedges or dashed lines contemplates each possible stereoisomer or mixture of stereoisomer (e.g., each enantiomer, each diastereomer, each meso compound, a racemic mixture, or scalemic mixture). Compounds Disclosed herein are compounds comprising phosphonopeptides or derivatives or salts thereof. For example, disclosed herein are compounds defined by Formula I: wherein R1is hydrogen, halide, substituted or unsubstituted C1-C20alkyl, substituted or unsubstituted C3-C20 cycloalkyl, substituted or unsubstituted C1-C20 alkoxy, substituted or unsubstituted C3-C20 aryl (e.g., substituted or unsubstituted phenyl), substituted or unsubstituted C4-C21alkylaryl, NRxRy, or ORa; R2is hydrogen, halide, substituted or unsubstituted C1-C20 alkyl, substituted or unsubstituted C3-C20 cycloalkyl, substituted or unsubstituted C1-C20 alkoxy, substituted or unsubstituted C3-C20aryl (e.g., substituted or unsubstituted phenyl), substituted or unsubstituted C4-C21 alkylaryl, NRxRy, or ORb; R3is hydrogen, hydroxyl, halide, substituted or unsubstituted C1-C20 alkyl, substituted or unsubstituted C1-C20acyl, substituted or unsubstituted C1-C20alkoxy, substituted or unsubstituted C1-C20amide, NRxRy, or one or more amino acids (e.g., one or more canonical or non-canonical amino acids); Raand Rbare each independently hydrogen, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C3-C10aryl (e.g., substituted or unsubstituted phenyl), or substituted or unsubstituted C4-C11 alkylaryl; and Rxand Ryare independently selected from hydrogen, or substituted or unsubstituted C1- C5alkyl, or substituted or unsubstituted C1-C5acyl; or a derivative or salt thereof. In some examples of Formula I, R1is ORaand / or R2is ORb. In some examples of Formula I, R1is ORaand / or R2is ORb, wherein Raand / or Rbis hydrogen. In some examples of Formula I, R3is one or more amino acids (e.g., one or more canonical or non-canonical amino acids). In some examples of Formula I, R3is one or more amino acids, each amino acid independently being selected from the group consisting of Arginine (Arg), Ne-hydroxyarginine, dehydro‐3‐methylaspartate, and Valine (Val). In some examples, the compound is defined by Formula II: wherein R3is hydrogen, hydroxyl, halide, substituted or unsubstituted C1-C20alkyl, substituted or unsubstituted C1-C20 acyl, substituted or unsubstituted C1-C20 alkoxy, substituted or unsubstituted C1-C20 amide, NRxRy, or one or more amino acids (e.g., one or more canonical or non-canonical amino acids); Raand Rbare each independently hydrogen, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C3-C10 aryl (e.g., substituted or unsubstituted phenyl), or substituted or unsubstituted C4-C11alkylaryl; and Rxand Ryare independently selected from hydrogen, or substituted or unsubstituted C1- C5 alkyl, or substituted or unsubstituted C1-C5 acyl; or a derivative or salt thereof. In some examples of Formula II, Raand / or Rbis hydrogen. In some examples of Formula II, Rais hydrogen. In some examples of Formula II, Rbis hydrogen. In some examples of Formula II, Raand Rbare both hydrogen. In some examples of Formula II, R3is one or more amino acids (e.g., one or more canonical or non-canonical amino acids). In some examples of Formula II, R3is one or more amino acids, each amino acid independently being selected from the group consisting of Arginine (Arg), Ne-hydroxyarginine, dehydro‐3‐methylaspartate, and Valine (Val). In some examples, the compound is defined by Formula III: wherein R3is hydrogen, hydroxyl, halide, substituted or unsubstituted C1-C20 alkyl, substituted or unsubstituted C1-C20acyl, substituted or unsubstituted C1-C20alkoxy, substituted or unsubstituted C1-C20amide, NRxRy, or one or more amino acids (e.g., one or more canonical or non-canonical amino acids); Rais hydrogen, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C3- C10aryl (e.g., substituted or unsubstituted phenyl), or substituted or unsubstituted C4-C11alkylaryl; and Rxand Ryare independently selected from hydrogen, or substituted or unsubstituted C1- C5alkyl, or substituted or unsubstituted C1-C5acyl; or a derivative or salt thereof. In some examples of Formula III, Rais hydrogen. In some examples of Formula III, R3is one or more amino acids (e.g., one or more canonical or non-canonical amino acids). In some examples of Formula III, R3is one or more amino acids, each amino acid independently being selected from the group consisting of Arginine (Arg), Ne-hydroxyarginine, dehydro‐3‐methylaspartate, and Valine (Val). In some examples of Formula III, Rais hydrogen and R3is one or more amino acids (e.g., one or more canonical or non-canonical amino acids). In some examples of Formula III, Rais hydrogen and R3is one or more amino acids, each amino acid independently being selected from the group consisting of Arginine (Arg), Ne-hydroxyarginine, dehydro‐3‐methylaspartate, and Valine (Val). In some examples, the compound is defined by Formula IV: wherein R3is hydrogen, hydroxyl, halide, substituted or unsubstituted C1-C20alkyl, substituted or unsubstituted C1-C20 acyl, substituted or unsubstituted C1-C20 alkoxy, substituted or unsubstituted C1-C20amide, NRxRy, or one or more amino acids (e.g., one or more canonical or non-canonical amino acids); and Rxand Ryare independently selected from hydrogen, or substituted or unsubstituted C1- C5 alkyl, or substituted or unsubstituted C1-C5 acyl; or a derivative or salt thereof. In some examples of Formula IV, R3is one or more amino acids (e.g., one or more canonical or non-canonical amino acids). In some examples of Formula IV, R3is one or more amino acids, each amino acid independently being selected from the group consisting of Arginine (Arg), Ne-hydroxyarginine, dehydro‐3‐methylaspartate, and Valine (Val). In some examples, the compound is defined by Formula V: wherein R4and R5are each independently hydrogen, hydroxyl, halide, substituted or unsubstituted C1-C20 alkyl, substituted or unsubstituted C1-C20 acyl, substituted or unsubstituted C1-C20 alkoxy, substituted or unsubstituted C1-C20amide, NRxRy, or one or more amino acids (e.g., one or more canonical or non-canonical amino acids); and Rxand Ryare independently selected from hydrogen, or substituted or unsubstituted C1- C5 alkyl, or substituted or unsubstituted C1-C5 acyl; or a derivative or salt thereof. In some examples of Formula V, R4and R5are each independently one or more amino acids (e.g., one or more canonical or non-canonical amino acids), or a derivative or salt thereof. In some examples of Formula V, wherein R4and R5are each independently one or more amino acids, each amino acid independently being selected from the group consisting of Arginine (Arg), Ne-hydroxyarginine, dehydro‐3‐methylaspartate, and Valine (Val), or a derivative or salt thereof. In some examples, the compound comprises AmPn-Arg-Val-DMA, AmPn-Ne- hydroxyarginine-Val-Ac, AmPn-Arg-Val-Ac, a derivative or salt thereof, or a combination thereof. In some examples, the compound is selected from the group consisting of: , , , derivatives or salts thereof, and combinations thereof. In some examples, the compound is selected from the group consisting of: , , , derivatives or salts thereof, and combinations thereof. In some examples, wherein the compound is selected from the group consisting of: , , derivatives or salts thereof, and combinations thereof. In some examples, the compound is selected from the group consisting of: , , or salts thereof, and combinations thereof. In some examples, the compound is a salt. In some examples, the compound is a salt form of Formula I, Formula II, Formula III, Formula IV, Formula V, or a combination thereof with a counterion. In some examples, the compound is a salt form of Formula II with a counterion. In some examples, the compound is a salt form of Formula II with a counterion and the salt form of the compound is selected from the group consisting of: and combinations thereof. In some examples, the counterion is a monovalent or divalent counterion. In some examples, the counterion is selected from the group consisting of sodium, potassium, calcium, lithium, magnesium, manganese, ammonium, iron, and combinations thereof. In some examples, the compound is a potassium salt, sodium salt, calcium salt, iron salt, ammonium salt, or a combination thereof. In some examples, the compound comprises an agriculturally acceptable salt thereof and / or a pharmaceutically acceptable salt thereof. In some examples, the compound is a tetra-peptide. In some examples, the compound is an isolate of a marine organism, or a derivative or salt thereof. In some examples, the compound is an actinobacterium isolate, or a derivative or salt thereof. In some examples, the compound is a Salinispora isolate or a derivative or salt thereof. In some examples, the compound is a Salinispora pacifica isolate or a derivative or salt thereof. Compositions Also disclosed herein are compositions comprising any of the compounds disclosed herein. In some examples, the compositions further comprise one or more agriculturally acceptable and / or pharmaceutically acceptable carriers. In some examples, the composition comprises a pharmaceutical composition, an agricultural composition, or a combination thereof. In some examples, the composition comprises a pesticide. In some examples, the composition comprises an herbicide. In some examples, the composition exhibits antimicrobial activity. In some examples, the composition results in at least 5 log reduction in a population of microbes. In some examples, the microbes are one or more microorganisms selected from the group consisting of gram negative bacteria. In some examples, the microbes are one or more microorganisms selected from the group consisting of Escherichia coli, Serratia marcescens, and Pantoea ananatis. In some examples, the composition is formulated for delivery to a plant or animal. In some examples, the composition is formulated for delivery to a plant. In some examples, the plant is a crop. In some examples, the plant is onions, such that the composition is formulated for delivery to onions. In some examples, the composition is formulated for delivery to an animal. In some examples, the animal is a companion animal, livestock, research animal, insect, or human. In some examples, the animal is an insect. In some examples, insect is a bee, such as a honeybee. Also disclosed herein are nucleic acids encoding any of the compounds or compositions disclosed herein. Also disclosed herein are vectors encoding said nucleic acids. Also disclosed herein are cells comprising said vectors. Also disclosed herein are cells comprising any of the compounds or compositions disclosed herein. In some examples, the cell comprises a marine organism cell. In some examples, the cell comprises an actinobacterium cell. In some examples, the cell comprises a Salinispora cell. In some examples, the cell comprises a Salinispora pacifica cell. Methods of Making and Use Also disclosed herein are methods of making any of the compounds disclosed herein. For example, the methods can comprise a biosynthetic method. In some examples, the method can use one or more enzymes derived from Salinispora, such as Salinispora pacifica. Also disclosed herein are methods of isolating and / or purifying a compound produced by a cell, wherein the compound comprises any of the compounds disclosed herein. In some examples, the cell comprises a marine organism cell. In some examples, the cell comprises an actinobacterium cell. In some examples, the cell comprises a Salinispora cell. In some examples, the cell comprises a Salinispora pacifica cell. Also disclosed herein are methods of use of any of the compounds, compositions, nucleic acids, vectors, and / or cells disclosed herein. For example, also disclosed herein are methods of using any of the compounds, compositions, nucleic acids, vectors, and / or cells as an antimicrobial, an herbicide, a pesticide, or combination thereof, for example to control (e.g., treat, reduce, inhibit, and / or ameliorate) an undesirable population. In some examples, the methods comprise using any of the compounds, compositions, nucleic acids, vectors, and / or cells as a pesticide. In some examples, the methods comprise using any of the compounds, compositions, nucleic acids, vectors, and / or cells to control (e.g., treat, reduce, inhibit, and / or ameliorate) an undesirable population in plants. In some examples, the method comprises contacting the plants or the locus thereof with or applying to the soil or water any of the compounds, compositions, nucleic acids, vectors, and / or cells. In some examples, the methods further comprise applying an additional pesticide. In some examples, the undesirable population is an herbicide resistant or tolerant population, a pesticide resistant or tolerant population, an antimicrobial resistant or tolerant population, or a combination thereof. In some examples, the undesirable population comprises bacteria. Also disclosed herein are methods of reducing the activity of bacteria, the methods comprising exposing the bacteria to an effective amount of any of the compounds, compositions, nucleic acids, vectors, and / or cells disclosed herein. Also disclosed herein are methods of reducing bacterial population, the method comprising exposing the bacteria to an effective amount of any of the compounds, compositions, nucleic acids, vectors, and / or cells disclosed herein. Also disclosed herein are methods of killing bacteria, the methods comprising exposing the bacteria to an effective amount of any of the compounds, compositions, nucleic acids, vectors, and / or cells disclosed herein. Also disclosed herein are methods of treating, preventing, and / or ameliorating a disease or a disorder in a plant or a subject in need thereof, the method comprising administering to the plant or subject a therapeutically effective amount of any of the compounds, compositions, nucleic acids, vectors, and / or cells disclosed herein. In some examples, the disease or disorder comprises an infection, such as with an infectious microbe (e.g., bacteria, virus, fungi, protozoa, etc.). In some examples, the disease or disorder comprises a microbial infection. Also disclosed herein are methods for treating, preventing, inhibiting, and / or ameliorating a microbial infection in a plant or a subject, comprising administering to the plant or subject an effective amount of any of the compounds, compositions, nucleic acids, vectors, and / or cells disclosed herein. In some examples, the microbial infection comprises a bacterial infection. In some examples, the bacteria comprise gram negative bacteria. In some examples, the bacteria comprise one or more bacteria selected from the group consisting of Escherichia coli, Serratia marcescens, and Pantoea ananatis. In some examples, the plant is a crop. In some examples, the plant is an onion. In some examples, the subject is an animal. In some examples, the animal is a companion animal, livestock, research animal, insect, or human. In some examples, the animal is an insect. In some examples, the insect is a bee, such as a honeybee. In some examples, the compound, composition, nucleic acid, and / or vector is delivered via cultured Salinispora pacifica. In some examples, the compounds, compositions, nucleic acids, vectors, and / or cells can display broad-spectrum antibacterial activity, with strong inhibition against pathogenic microbes. The methods of treatment of the disease or disorder described herein can further include treatment with one or more additional agents. The one or more additional agents and the compounds and compositions or pharmaceutically acceptable salts thereof as described herein can be administered in any order, including simultaneous administration, as well as temporally spaced order of up to several days apart. The methods can also include more than a single administration of the one or more additional agents and / or the compounds and compositions or pharmaceutically acceptable salts thereof as described herein. The administration of the one or more additional agents and the compounds and compositions or pharmaceutically acceptable salts thereof as described herein can be by the same or different routes. When treating with one or more additional agents, the compounds and compositions or pharmaceutically acceptable salts thereof as described herein can be combined into a pharmaceutical composition that includes the one or more additional agents. It is understood, however, that the specific dose level for any particular subject will depend upon a variety of factors. Such factors include the age, body weight, general health, sex, and diet of the subject. Other factors include the time and route of administration, rate of excretion, drug combination, and the type and severity of the particular disease or disorder. The methods, compounds, and compositions as described herein are useful for both prophylactic and therapeutic treatment. As used herein the term treating or treatment includes prevention; delay in onset; diminution, eradication, or delay in exacerbation of signs or symptoms after onset; and prevention of relapse. For prophylactic use, a therapeutically effective amount of the compounds and compositions or pharmaceutically acceptable salts thereof as described herein are administered to a subject prior to onset (e.g., before obvious signs of the disease or disorder), during early onset (e.g., upon initial signs and symptoms of the disease or disorder), or after an established development of the disease or disorder. Prophylactic administration can occur for several days to years prior to the manifestation of symptoms of a disease or disorder. Therapeutic treatment involves administering to a subject a therapeutically effective amount of the compounds and compositions or pharmaceutically acceptable salts thereof as described herein after the disease or disorder is diagnosed. Pharmaceutical Compositions Also disclosed herein are pharmaceutical compositions comprising any of the compounds or compositions disclosed herein. In some examples, the pharmaceutical composition is administered to a subject. In some examples, the subject is an animal. In some examples, the animal is a companion animal, livestock, research animal, insect, or human. In some examples, the animal is an insect. In some examples, the insect is a bee, such as a honeybee. In some examples, the disclosed compositions comprise the disclosed compounds (including pharmaceutically acceptable salt(s) thereof) as an active ingredient, a pharmaceutically acceptable carrier, and, optionally, other therapeutic ingredients or adjuvants. The instant compositions include those suitable for oral, rectal, topical, and parenteral (including subcutaneous, intramuscular, and intravenous) administration, although the most suitable route in any given case will depend on the particular host, and nature and severity of the conditions for which the active ingredient is being administered. The compositions can be conveniently presented in unit dosage form and prepared by any of the methods well known in the art of pharmacy. Pharmaceutical Compositions, Formulations, Methods of Administration, and Kits In vivo application of the disclosed compounds, and compositions containing them, can be accomplished by any suitable method and technique presently or prospectively known to those skilled in the art. For example, the disclosed compounds can be formulated in a physiologically- or pharmaceutically-acceptable form and administered by any suitable route known in the art including, for example, oral, nasal, rectal, topical, and parenteral routes of administration. As used herein, the term parenteral includes subcutaneous, intradermal, intravenous, intramuscular, intraperitoneal, and intrasternal administration, such as by injection. Administration of the disclosed compounds or compositions can be a single administration, or at continuous or distinct intervals as can be readily determined by a person skilled in the art. The compounds disclosed herein, and compositions comprising them, can also be administered utilizing liposome technology, slow release capsules, implantable pumps, and biodegradable containers. These delivery methods can, advantageously, provide a uniform dosage over an extended period of time. The compounds can also be administered in their salt derivative forms or crystalline forms. The compounds disclosed herein can be formulated according to known methods for preparing pharmaceutically acceptable compositions. Formulations are described in detail in a number of sources which are well known and readily available to those skilled in the art. For example, Remington’s Pharmaceutical Science by E.W. Martin (1995) describes formulations that can be used in connection with the disclosed methods. In general, the compounds disclosed herein can be formulated such that an effective amount of the compound is combined with a suitable excipient in order to facilitate effective administration of the compound. The compositions used can also be in a variety of forms. These include, for example, solid, semi- solid, and liquid dosage forms, such as tablets, pills, powders, liquid solutions or suspension, suppositories, injectable and infusible solutions, and sprays. The preferred form depends on the intended mode of administration and application. The compositions can also include conventional pharmaceutically-acceptable carriers and diluents which are known to those skilled in the art. Examples of carriers or diluents for use with the compounds include ethanol, dimethyl sulfoxide, glycerol, alumina, starch, saline, and equivalent carriers and diluents. To provide for the administration of such dosages for the desired application, compositions disclosed herein can comprise between about 0.1% and 100% by weight of the total of one or more of the subject compounds based on the weight of the total composition including carrier or diluent. The pharmaceutical carrier employed can be, for example, a solid, liquid, or gas. Examples of solid carriers include lactose, terra alba, sucrose, talc, gelatin, agar, pectin, acacia, magnesium stearate, and stearic acid. Examples of liquid carriers are sugar syrup, peanut oil, olive oil, and water. Examples of gaseous carriers include carbon dioxide and nitrogen. Formulations suitable for administration include, for example, aqueous sterile injection solutions, which can contain antioxidants, buffers, bacteriostats, and solutes that render the formulation isotonic with the blood of the intended recipient; and aqueous and nonaqueous sterile suspensions, which can include suspending agents and thickening agents. The formulations can be presented in unit-dose or multi-dose containers, for example sealed ampoules and vials, and can be stored in a freeze dried (lyophilized) condition requiring only the condition of the sterile liquid carrier, for example, water for injections, prior to use. Extemporaneous injection solutions and suspensions can be prepared from sterile powder, granules, tablets, etc. It should be understood that in addition to the excipients particularly mentioned above, the compositions disclosed herein can include other agents conventional in the art having regard to the type of formulation in question. Compounds disclosed herein, and compositions comprising them, can be delivered to a cell either through direct contact with the cell or via a carrier means. Carrier means for delivering compounds and compositions to cells are known in the art. For the treatment of oncological disorders, the compounds or compositions disclosed herein can be administered to a patient in need of treatment in combination with other substances and / or therapies and / or with surgical treatment. These other substances or treatments can be given at the same as or at different times from the compounds or compositions disclosed herein. In certain examples, compounds and compositions disclosed herein can be locally administered at one or more anatomical sites, such as sites of microbial infection, optionally in combination with a pharmaceutically acceptable carrier such as an inert diluent. Compounds and compositions disclosed herein can be systemically administered, such as intravenously or orally, optionally in combination with a pharmaceutically acceptable carrier such as an inert diluent, or an assimilable edible carrier for oral delivery. They can be enclosed in hard or soft shell gelatin capsules, can be compressed into tablets, or can be incorporated directly with the food of the patient’s diet. For oral therapeutic administration, the active compound can be combined with one or more excipients and used in the form of ingestible tablets, buccal tablets, troches, capsules, elixirs, suspensions, syrups, wafers, aerosol sprays, and the like. The tablets, troches, pills, capsules, and the like can also contain the following: binders such as gum tragacanth, acacia, corn starch or gelatin; diluents such as dicalcium phosphate; a disintegrating agent such as corn starch, potato starch, alginic acid and the like; a lubricant such as magnesium stearate; and a sweetening agent such as sucrose, fructose, lactose or aspartame or a flavoring agent such as peppermint, oil of wintergreen, or cherry flavoring can be added. When the unit dosage form is a capsule, it can contain, in addition to materials of the above type, a liquid carrier, such as a vegetable oil or a polyethylene glycol. Various other materials can be present as coatings or to otherwise modify the physical form of the solid unit dosage form. For instance, tablets, pills, or capsules can be coated with gelatin, wax, shellac, or sugar and the like. A syrup or elixir can contain the active compound, sucrose or fructose as a sweetening agent, methyl and propylparabens as preservatives, a dye and flavoring such as cherry or orange flavor. Of course, any material used in preparing any unit dosage form should be pharmaceutically acceptable and substantially non-toxic in the amounts employed. In addition, the active compound can be incorporated into sustained-release preparations and devices. Compounds and compositions disclosed herein, including pharmaceutically acceptable salts thereof, can be administered intravenously, intramuscularly, or intraperitoneally by infusion or injection. Solutions of the active agent or its salts can be prepared in water, optionally mixed with a nontoxic surfactant. Dispersions can also be prepared in glycerol, liquid polyethylene glycols, triacetin, and mixtures thereof and in oils. Under ordinary conditions of storage and use, these preparations can contain a preservative to prevent the growth of microorganisms. The pharmaceutical dosage forms suitable for injection or infusion can include sterile aqueous solutions or dispersions or sterile powders comprising the active ingredient, which are adapted for the extemporaneous preparation of sterile injectable or infusible solutions or dispersions, optionally encapsulated in liposomes. The ultimate dosage form should be sterile, fluid and stable under the conditions of manufacture and storage. The liquid carrier or vehicle can be a solvent or liquid dispersion medium comprising, for example, water, ethanol, a polyol (for example, glycerol, propylene glycol, liquid polyethylene glycols, and the like), vegetable oils, nontoxic glyceryl esters, and suitable mixtures thereof. The proper fluidity can be maintained, for example, by the formation of liposomes, by the maintenance of the required particle size in the case of dispersions or by the use of surfactants. Optionally, the prevention of the action of microorganisms can be brought about by various other antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, thimerosal, and the like. In many cases, it will be preferable to include isotonic agents, for example, sugars, buffers or sodium chloride. Prolonged absorption of the injectable compositions can be brought about by the inclusion of agents that delay absorption, for example, aluminum monostearate and gelatin. Pharmaceutical compositions disclosed herein suitable for injectable use include sterile aqueous solutions or dispersions. Furthermore, the compositions can be in the form of sterile powders for the extemporaneous preparation of such sterile injectable solutions or dispersions. In some examples, the final injectable form can be sterile and can be effectively fluid for easy syringability. In some examples, the pharmaceutical compositions can be stable under the conditions of manufacture and storage; thus, they can be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (e.g., glycerol, propylene glycol and liquid polyethylene glycol), vegetable oils, and suitable mixtures thereof. Sterile injectable solutions are prepared by incorporating a compound and / or agent disclosed herein in the required amount in the appropriate solvent with various other ingredients enumerated above, as required, followed by filter sterilization. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred methods of preparation are vacuum drying and freeze-drying techniques, which yield a powder of the active ingredient plus any additional desired ingredient present in the previously sterile-filtered solutions. Pharmaceutical compositions disclosed herein can be in a form suitable for topical use such as, for example, an aerosol, cream, ointment, lotion, dusting powder, mouth washes, gargles, solution, tincture, and the like. In some examples, the compositions can be in a form suitable for use in transdermal devices. In some examples, it will be desirable to administer them topically to the skin as compositions, in combination with a dermatologically acceptable carrier, which can be a solid or a liquid. Compounds and agents and compositions disclosed herein can be applied topically to a subject’s skin. These formulations can be prepared, utilizing any of the compounds disclosed herein or pharmaceutically acceptable salts thereof, via conventional processing methods. Useful solid carriers include finely divided solids such as talc, clay, microcrystalline cellulose, silica, alumina and the like. Useful liquid carriers include water, alcohols or glycols or water-alcohol / glycol blends, in which the compounds can be dissolved or dispersed at effective levels, optionally with the aid of non-toxic surfactants. Adjuvants such as fragrances and additional antimicrobial agents can be added to optimize the properties for a given use. The resultant liquid compositions can be applied from absorbent pads, used to impregnate bandages and other dressings, or sprayed onto the affected area using pump-type or aerosol sprayers, for example. Thickeners such as synthetic polymers, fatty acids, fatty acid salts and esters, fatty alcohols, modified celluloses or modified mineral materials can also be employed with liquid carriers to form spreadable pastes, gels, ointments, soaps, and the like, for application directly to the skin of the user. Pharmaceutical compositions disclosed herein can be in a form suitable for rectal administration wherein the carrier is a solid. In some examples, the mixture forms unit dose suppositories. Suitable carriers include cocoa butter and other materials commonly used in the art. The suppositories can be conveniently formed by first admixing the composition with the softened or melted carriers) followed by chilling and shaping in molds. In addition to the aforementioned carrier ingredients, the pharmaceutical formulations described above can include, as appropriate, one or more additional carrier ingredients such as diluents, buffers, flavoring agents, binders, surface-active agents, thickeners, lubricants, preservatives (including anti-oxidants) and the like. Furthermore, other adjuvants can be included to render the formulation isotonic with the blood of the intended recipient. Compositions containing any of the compounds disclosed herein, and / or pharmaceutically acceptable salts thereof, can also be prepared in powder or liquid concentrate form. Useful dosages of the compounds and agents and pharmaceutical compositions disclosed herein can be determined by comparing their in vitro activity, and in vivo activity in animal models. Methods for the extrapolation of effective dosages in mice, and other animals, to humans are known to the art. The dosage ranges for the administration of the compositions are those large enough to produce the desired effect in which the symptoms or disorder are affected. The dosage should not be so large as to cause adverse side effects, such as unwanted cross-reactions, anaphylactic reactions, and the like. Generally, the dosage will vary with the age, condition, sex and extent of the disease in the patient and can be determined by one of skill in the art. The dosage can be adjusted by the individual physician in the event of any counterindications. Dosage can vary, and can be administered in one or more dose administrations daily, for one or several days. Also disclosed are kits that comprise a compound disclosed herein in one or more containers. The disclosed kits can optionally include pharmaceutically acceptable carriers and / or diluents. In one embodiment, a kit includes one or more other components, adjuncts, or adjuvants as described herein. In one embodiment, a kit includes instructions or packaging materials that describe how to administer a compound or composition of the kit. Containers of the kit can be of any suitable material, e.g., glass, plastic, metal, etc., and of any suitable size, shape, or configuration. In one embodiment, a compound and / or agent disclosed herein is provided in the kit as a solid, such as a tablet, pill, or powder form. In another embodiment, a compound and / or agent disclosed herein is provided in the kit as a liquid or solution. In one embodiment, the kit comprises an ampoule or syringe containing a compound and / or agent disclosed herein in liquid or solution form. In some examples, the kit further comprises at least one agent, wherein the compound and the agent are co-formulated. In some examples, the compound and the agent are co-packaged. The kits can also comprise compounds and / or products co-packaged, co-formulated, and / or co-delivered with other components. For example, a drug manufacturer, a drug reseller, a physician, a compounding shop, or a pharmacist can provide a kit comprising a disclosed compound and / or product and another component for delivery to a patient. It is contemplated that the disclosed kits can be used in connection with the disclosed methods of making, the disclosed methods of using, and / or the disclosed compositions. Agricultural Compositions, Formulations, and Methods of Administration Also disclosed herein are agricultural compositions comprising any of the compounds or compositions disclosed herein, and methods of use thereof. For example, the compound or composition can be applied to vegetation or an area adjacent the vegetation or applied to soil or water to prevent the emergence or growth of vegetation in an amount sufficient to induce an effect, such as an antimicrobial effect. In some embodiments, compounds or compositions are used in an amount sufficient to induce an antimicrobial effect while still showing good crop compatibility. The present disclosure also relates to formulations of the compositions and methods disclosed herein. In some embodiments, the formulation can be in the form of a single package formulation including any of the compounds disclosed herein. In some embodiments, the formulation can be in the form of a single package formulation including any of the compounds disclosed herein and further including at least one additive. In some embodiments, the formulation can be in the form of a two-package formulation, wherein one package contains any of the compounds disclosed herein and while the other package contains at least one additive. In some embodiments of the two-package formulation, the formulation including any of the compounds disclosed herein and the formulation including at least one additive are mixed before application and then applied simultaneously. In some embodiments, the mixing is performed as a tank mix (i.e., the formulations are mixed immediately before or upon dilution with water). In some embodiments, the formulation including (a) and the formulation including (b) are not mixed but are applied sequentially (in succession), for example, immediately or within 1 hour, within 2 hours, within 4 hours, within 8 hours, within 16 hours, within 24 hours, within 2 days, or within 3 days, of each other. In some embodiments, the formulation of any of the compounds disclosed herein is present in suspended, emulsified, or dissolved form. Exemplary formulations include, but are not limited to, aqueous solutions, powders, suspensions, also highly-concentrated aqueous, oily or other suspensions or dispersions, aqueous emulsions, aqueous microemulsions, aqueous suspo- emulsions, oil dispersions, self-emulsifying formulations, pastes, dusts, and materials for spreading or granules. In some embodiments, the compound or composition is an aqueous solution that can be diluted before use. In some embodiments, the compound or composition is provided as a high- strength formulation such as a concentrate. In some embodiments, the concentrate is stable and retains potency during storage and shipping. In some embodiments, the concentrate is a clear, homogeneous liquid that is stable at temperatures of 54 °C or greater. In some embodiments, the concentrate does not exhibit any precipitation of solids at temperatures of -10 °C or higher. In some embodiments, the concentrate does not exhibit separation, precipitation, or crystallization of any components at low temperatures. For example, the concentrate remains a clear solution at temperatures below 0 °C (e.g., below -5 °C, below -10 °C, below -15 °C). In some embodiments, the concentrate exhibits a viscosity of less than 50 centipoise (50 megapascals), even at temperatures as low as 5 °C. The compositions and methods disclosed herein can also be mixed with or applied with an additive. In some embodiments, the additive can be diluted in water or can be concentrated. In some embodiments, the additive is added sequentially. In some embodiments, the additive is added simultaneously. In some embodiments, the additive is premixed with the compound. In some embodiments, the additive is an additional pesticide. For example, the compositions described herein can be applied in conjunction with one or more additional pesticides. The composition can be formulated with the one or more additional pesticides, tank mixed with the one or more additional pesticides, or applied sequentially with the one or more additional pesticides. In some embodiments, the additional pesticide or an agriculturally acceptable salt or ester thereof is provided in a premixed formulation with the compound. In some embodiments, the additive includes an agriculturally acceptable adjuvant. Exemplary agriculturally acceptable adjuvants include, but are not limited to, antifreeze agents, antifoam agents, compatibilizing agents, sequestering agents, neutralizing agents and buffers, corrosion inhibitors, colorants, odorants, penetration aids, wetting agents, spreading agents, dispersing agents, thickening agents, freeze point depressants, antimicrobial agents, crop oil, herbicide safeners, adhesives (for instance, for use in seed formulations), surfactants, protective colloids, emulsifiers, tackifiers, and mixtures thereof. Exemplary agriculturally acceptable adjuvants include, but are not limited to, crop oil concentrate (mineral oil (85%) +emulsifiers (15%)); nonylphenol ethoxylate; benzylcocoalkyldimethyl quaternary ammonium salt; blend of petroleum hydrocarbon, alkyl esters, organic acid, and anionic surfactant; C9-C11alkylpolyglycoside; phosphate alcohol ethoxylate; natural primary alcohol (C12-C16) ethoxylate or less, di-sec-butylphenol EO-PO block copolymer; polysiloxane-methyl cap; nonylphenol ethoxylate+urea ammonium nitrate; emulsified methylated seed oil; tridecyl alcohol (synthetic) ethoxylate (8 EO); tallow amine ethoxylate (15 EO); and PEG(400) dioleate-99. In some embodiments, the additive is a safener, which is an organic compound leading to better crop plant compatibility when applied with a pesticide. In some embodiments, the safener itself is herbicidally active. In some embodiments, the safener acts as an antidote or antagonist in the crop plants and can reduce or prevent damage to the crop plants. Exemplary surfactants (e.g., wetting agents, tackifiers, dispersants, emulsifiers) include, but are not limited to, the alkali metal salts, alkaline earth metal salts and ammonium salts of aromatic sulfonic acids, for example lignosulfonic acids, phenolsulfonic acids, naphthalenesulfonic acids, and dibutylnaphthalenesulfonic acid, and of fatty acids, alkyl- and alkylarylsulfonates, alkyl sulfates, lauryl ether sulfates and fatty alcohol sulfates, and salts of sulfated hexa-, hepta- and octadecanols, and also of fatty alcohol glycol ethers, condensates of sulfonated naphthalene and its derivatives with formaldehyde, condensates of naphthalene or of the naphthalene sulfonic acids with phenol and formaldehyde, polyoxyethylene octylphenol ether, ethoxylated isooctyl-, octyl- or nonylphenol, alkylphenyl or tributylphenyl polyglycol ether, alkyl aryl polyether alcohols, isotridecyl alcohol, fatty alcohol / ethylene oxide condensates, ethoxylated castor oil, polyoxyethylene alkyl ethers or polyoxypropylene alkyl ethers, lauryl alcohol polyglycol ether acetate, sorbitol esters, lignosulfite waste liquors and proteins, denatured proteins, polysaccharides (e.g., methylcellulose), hydrophobically modified starches, polyvinyl alcohol, polycarboxylates, polyalkoxylates, polyvinyl amine, polyethyleneimine, polyvinylpyrrolidone and copolymers thereof. Exemplary thickeners include, but are not limited to, polysaccharides, such as xanthan gum, and organic and inorganic sheet minerals, and mixtures thereof. Exemplary antifoam agents include, but are not limited to, silicone emulsions, long-chain alcohols, fatty acids, salts of fatty acids, organofluorine compounds, and mixtures thereof. Exemplary antimicrobial agents include, but are not limited to, bactericides based on dichlorophen and benzyl alcohol hemiformal, and isothiazolinone derivatives, such as alkylisothiazolinones and benzisothiazolinones, and mixtures thereof. Exemplary antifreeze agents include, but are not limited to ethylene glycol, propylene glycol, urea, glycerol, and mixtures thereof. Exemplary colorants include, but are not limited to, the dyes known under the names Rhodamine B, pigment blue 15:4, pigment blue 15:3, pigment blue 15:2, pigment blue 15:1, pigment blue 80, pigment yellow 1, pigment yellow 13, pigment red 112, pigment red 48:2, pigment red 48:1, pigment red 57:1, pigment red 53:1, pigment orange 43, pigment orange 34, pigment orange 5, pigment green 36, pigment green 7, pigment white 6, pigment brown 25, basic violet 10, basic violet 49, acid red 51, acid red 52, acid red 14, acid blue 9, acid yellow 23, basic red 10, basic red 108, and mixtures thereof. Exemplary adhesives include, but are not limited to, polyvinylpyrrolidone, polyvinyl acetate, polyvinyl alcohol, tylose, and mixtures thereof. In some embodiments, the additive includes a carrier. In some embodiments, the additive includes a liquid or solid carrier. In some embodiments, the additive includes an organic or inorganic carrier. Exemplary liquid carriers include, but are not limited to, petroleum fractions or hydrocarbons such as mineral oil, aromatic solvents, paraffinic oils, and the like or less, vegetable oils such as soybean oil, rapeseed oil, olive oil, castor oil, sunflower seed oil, coconut oil, corn oil, cottonseed oil, linseed oil, palm oil, peanut oil, safflower oil, sesame oil, tung oil and the like or less, esters of the above vegetable oils or less, esters of monoalcohols or dihydric, trihydric, or other lower polyalcohols (4-6 hydroxy containing), such as 2-ethyl hexyl stearate, n- butyl oleate, isopropyl myristate, propylene glycol dioleate, di-octyl succinate, di-butyl adipate, di-octyl phthalate and the like or less, esters of mono, di and polycarboxylic acids and the like, toluene, xylene, petroleum naphtha, crop oil, acetone, methyl ethyl ketone, cyclohexanone, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, propylene glycol monomethyl ether and diethylene glycol monomethyl ether, methyl alcohol, ethyl alcohol, isopropyl alcohol, amyl alcohol, ethylene glycol, propylene glycol, glycerine, N-methyl-2- pyrrolidinone, N,N-dimethyl alkylamides, dimethyl sulfoxide, liquid fertilizers and the like, and water as well as mixtures thereof. Exemplary solid carriers include, but are not limited to, silicas, silica gels, silicates, talc, kaolin, limestone, lime, chalk, bole, loess, clay, dolomite, diatomaceous earth, calcium sulfate, magnesium sulfate, magnesium oxide, ground synthetic materials, pyrophyllite clay, attapulgus clay, kieselguhr, calcium carbonate, bentonite clay, Fuller's earth, cottonseed hulls, wheat flour, soybean flour, pumice, wood flour, walnut shell flour, lignin, ammonium sulfate, ammonium phosphate, ammonium nitrate, ureas, cereal meal, tree bark meal, wood meal and nutshell meal, cellulose powders, and mixtures thereof. In some embodiments, emulsions, pastes or oil dispersions can be prepared by homogenizing the compound in water by means of wetting agent, tackifier, dispersant or emulsifier. In some embodiments, concentrates suitable for dilution with water are prepared, comprising the compound, a wetting agent, a tackifier, and a dispersant or emulsifier. In some embodiments, powders or materials for spreading and dusts can be prepared by mixing or concomitant grinding of the compound and optionally a safener with a solid carrier. In some embodiments, granules (e.g., coated granules, impregnated granules and homogeneous granules) can be prepared by binding the compound to solid carriers. The compositions disclosed herein can be applied in any known technique for applying pesticides. Exemplary application techniques include, but are not limited to, spraying, atomizing, dusting, spreading, or direct application into water (in-water). The method of application can vary depending on the intended purpose. In some embodiments, the method of application can be chosen to ensure the finest possible distribution of the compositions disclosed herein. If desired, the compositions can be applied as an in-water application. When the compositions are used in crops, the compositions can be applied after seeding and before or after the emergence of the crop plants. In some embodiments, when the compositions are used in crops, the compositions can be applied before seeding of the crop plants. In some embodiments, the compositions disclosed herein are applied to vegetation or an area adjacent the vegetation or applied to soil or water by spraying (e.g., foliar spraying). In some embodiments, the spraying techniques use, for example, water as carrier and spray liquor rates of from 10 liters per hectare (L / ha) to 2000 L / ha (e.g., from 50 L / ha to 1000 L / ha, or from 100 to 500 L / ha). In some embodiments, the compositions disclosed herein are applied by the low-volume or the ultra-low-volume method, wherein the application is in the form of micro granules. In some embodiments, wherein the compositions disclosed herein are less well tolerated by certain crop plants, the compositions can be applied with the aid of the spray apparatus in such a way that they come into little contact, if any, with the leaves of the sensitive crop plants while reaching the undesirable population or the bare soil (e.g., post-directed or lay- by). In some embodiments, the compositions disclosed herein can be applied as dry formulations (e.g., granules, WDGs, etc.) into water. The compositions and methods disclosed herein can also be used in plants that are resistant to, for instance, pesticides, pathogens, and / or insects. In some embodiments, the compositions and methods disclosed herein can be used in plants that are resistant to one or more pesticides because of genetic engineering or breeding. In some embodiments, the compositions described herein and other complementary pesticides are applied at the same time, either as a combination formulation or as a tank mix, or as sequential applications. The compositions and methods may be used in controlling undesirable populations in crops possessing agronomic stress tolerance (including but not limited to drought, cold, heat, salt, water, nutrient, fertility, pH), pest tolerance (including but not limited to insects, fungi and pathogens) and crop improvement traits (including but not limited to yield; protein, carbohydrate, or oil content; protein, carbohydrate, or oil composition; plant stature and plant architecture). The herbicidal compositions described herein can be used to control herbicide resistant or tolerant populations. The methods employing the compositions described herein may also be employed to control herbicide resistant or tolerant populations. Exemplary resistant or tolerant populations include, but are not limited to, biotypes with resistance or tolerance to multiple herbicides, biotypes with resistance or tolerance to multiple chemical classes, biotypes with resistance or tolerance to multiple herbicide modes-of-action, and biotypes with multiple resistance or tolerance mechanisms (e.g., target site resistance or metabolic resistance). The present compositions may be formulated and delivered to host plants by methods known in the art, including soil drench via soil drench formulations, seed inoculation via seed inoculation formulations, and plant inoculation via plant inoculation formulations. Seed inoculation formulations can include a carrier such as peat slurry or a film coat consisting of alginate polymers, to protect the compositions from environmental stresses such as desiccation and temperature perturbations. Soil drench or in-furrow composition delivery to plants may be performed by applying the compositions and / or composition formulations in soil before or after planting. Soil drench has several advantages over seed inoculation: 1) prevents the compositions or composition formulations from being inhibited by the chemicals coated on seeds (e.g., fungicides and pesticides) and 2) delivers compositions or composition formulations at higher density without being constrained by seed size. A higher composition or composition formulation concentration is usually required for soil inoculation. Foliar spray and root dipping are also suitable for composition or composition formulation delivery of plants. Plants may be treated at the seedling stage to increase persistence in the plant. In addition, seedling priming, direct seed coating, alginate seed coating, and 12-h coating are within the scope of the present disclosure. The compositions in the present invention may be formulated and administered to insect hives as a liquid suspension, powder, or solid substrates, such as lipid-based patties. Liquid formulations may optionally comprise water, sugar syrup and / or other carbohydrate, vitamins, stabilizers, and any other nutrients supportive of bee health. Dry formulations may optionally comprise powdered sugar or other carbohydrate, vitamins, stabilizers, and any other nutrients supportive of bee health. Patty formulations may comprise sugar and / or other carbohydrate, vegetable and / or animal fat, vitamins, stabilizers, and any other nutrients supportive of bee health. The compositions may be administered as a treatment and / or prophylactically. The compositions may also be administered as a protocol that includes vaccination, phage therapy, the use of lactic acid-producing bacteria. The formulations optionally include additional foulbrood treatments, such as tylosin tartrate (produced by Elanco, e.g., tylosin A, B, C, and D), and / or Terramycin® (produced by Pfizer, e.g. TM25®, TM50®, TM100®), including Terra-Pro®, and / or the active ingredient of Terramycin®, oxytetracycline HCL. For example, the compounds and compositions disclosed herein can be formulated and / or used in conjunction with the known foulbrood treatments. Therefore, the methods include treatment with one or more of the present compositions and can optionally include additional treatments from previously-known modalities. A number of embodiments of the invention have been described. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of the invention. Accordingly, other embodiments are within the scope of the following claims. The examples below are intended to further illustrate certain aspects of the systems and methods described herein, and are not intended to limit the scope of the claims. EXAMPLES The following examples are set forth below to illustrate the methods and results according to the disclosed subject matter. These examples are not intended to be inclusive of all aspects of the subject matter disclosed herein, but rather to illustrate representative methods and results. These examples are not intended to exclude equivalents and variations of the present invention which are apparent to one skilled in the art. Efforts have been made to ensure accuracy with respect to numbers (e.g., amounts, temperature, etc.) but some errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, temperature is in °C or is at ambient temperature, and pressure is at or near atmospheric. There are numerous variations and combinations of measurement conditions, e.g., component concentrations, temperatures, pressures and other measurement ranges and conditions that can be used to optimize the described process. Example 1 - Peptide Inhibitors Comprising Combinations of Non‐Canonical Amino Acids Described herein is a means to obtain a series of antimicrobial peptides and their application as antimicrobial agents is demonstrated against agricultural and animal pathogens. Inhibition of gram negative bacteria include the pathogen of onions, a major commercial crop for which there are no bactericides on market, pathogen of the American honeybee (critical industrial pollination insect), and pathogens of human and animals. Thus, there is potential utility for both pharmaceutical and agricultural applications. The compounds comprise combinations of standard and non‐canonical amino acids. Incorporation of dehydo‐3‐ methylaspartate (DHMA), an amino acid previously unknown to Nature, increased the activity of compound 1. The vinyl moiety of DHMA provides a means for reactivity‐ based discovery of other compounds containing this amino acid, and chemical diversification of such compounds by synthetic or enzymatic means (potential substitutions, additions, cycloadditions). Example 2 - Genomics Accelerated Discovery of Antimicrobial Natural Products from Bacteria The emergence and spread of antimicrobial resistance (AMR) has created an urgent need for new antibiotics. Despite the looming threat of AMR, the antimicrobial drug development pipeline is sparse, and without action, return to a pre-antibiotic era is conceivable. Microbial natural products are the source of most clinically used antibiotics, and continue to be an excellent source of lead compounds. Further, the advent of genomics and detection of natural product biosynthetic gene clusters (BGCs) has revolutionized the study of microbial metabolism, making possible the targeted discovery of chemically unusual and biologically active compounds. Phosphonate natural products are defined by a direct C-P bond, and are renowned for their inhibitory properties. The phosphonate moiety is analogous to carboxylate and phosphate ester functional groups on primary metabolites, enabling chemical mimicry and competitive or suicide inhibition of essential metabolic enzymes. Biosynthesis of nearly all known phosphonates is initiated by phosphoenolpyruvate mutase (PepM), which catalyzes the isomerization of phosphoenolpyruvate to phosphonopyruvate, forming the characteristic C-P bond. Further, genes involved in phosphonate biosynthesis tend to co-localize with pepM on the genome of the producing organism in BGCs. Genome mining has proven to be an invaluable tool in phosphonate discovery efforts, enabling the targeted discovery of unprecedented enzymatic transformations and metabolites. Terrestrial microbes are the producers of most known phosphonates, with fewer studies focusing on the phosphonate metabolism of marine organisms. A phosphonate BGC encoded by the marine actinobacterium Salinispora pacifica was detected. Heterologous expression of this BGC enabled the isolation and chemical characterization of salinisporaphos A-C , a series of aminomethylphosphonate-containing phosphonopeptides. Salinisporaphos A was shown to contain an amino acid unprecedented in Nature, which was identified as dehydromethylaspartate. Salinisporaphos A and B were shown to have antimicrobial activity against select Gram-negative bacteria. Collectively, discovery of these phosphonates expands the knowledge of phosphonate metabolism in taxonomically diverse bacteria. Example 3 - Discovery of Antimicrobial Phosphonopeptide Natural Products from Salinispora pacifica by Genome Mining Abstract. Phosphonate natural products, defined by a direct carbon-phosphorous bond, are known for their ability to potently inhibit essential metabolism in plants and microbes, which has driven their development as herbicides and antibiotics, respectively. Most phosphonate natural products have been isolated from terrestrial microbes, particularly those residing in soil. Comparatively, less is known about the phosphonate metabolism of marine organisms. Actinobacteria are storied producers of bioactive natural products, including most clinically used antibiotics. While mining actinobacterial genomes, a phosphonate biosynthetic gene cluster was detected in the obligate marine actinobacterium Salinispora pacifica. Heterologous expression of this cluster enabled the isolation and structure elucidation of several new phosphonopeptides, which named herein as salinisporaphos A-C. Salinisporaphos A was shown to contain an amino acid unprecedented in nature, which was identified as dehydromeththylaspartate (DHMA). Salinisporaphos A and B exhibited narrow spectrum antimicrobial activity against select Gram- negative bacteria, including Escherichia coli, Serratia marcescens, and Pantoea ananatis. This work expands knowledge of phosphonate metabolism in marine microbes, and demonstrates the importance of investigating underexplored ecological niches in phosphonate discovery efforts. Introduction. Phosphonate natural products (Pns) are known to be potent inhibitors of essential metabolic pathways in microbes, plants, and humans. In turn, numerous natural products (NPs) of this chemical class have been developed as antimicrobials, herbicides, and pharmaceuticals. Notable examples include fosfomycin (Monurol), a broad spectrum antibiotic prescribed to treat urinary tract infections, phosphinothricin, a potent herbicide used globally in commercial agriculture, and K-26, a preclinical antihypertensive agent [1-3]. The biological activity of phosphonates is often attributed to their hallmark C-P bond. This moiety is analogous to phosphate ester and carboxylate groups on primary metabolites, enabling chemical mimicry and inhibition of their cognate enzymes [4]. These antimetabolite properties continue to drive interest in phosphonate discovery and the isolation of novel and bioactive compounds. Recently, targeted discovery of phosphonates has been made possible through genome mining [5]. Phosphoenolypyruvate mutase (PepM) catalyzes a globally conserved first step in phosphonate biosynthesis, the isomerization of phosphoenolpyruvate (PEP) to phosphonopyruvate (PnPy) [6]. Thus, pepM serves as a marker to identify strains with the biosynthetic potential for phosphonate natural products and dereplicate and prioritize candidate biosynthetic gene clusters (BGCs) for investigation. This approach has enabled the high- throughput discovery of numerous biologically active and chemically unusual phosphonate natural products. Argolaphos is a broad spectrum antimicrobial containing the non-canonical amino acids aminomethylphosphonate (AmPn) and Ne-hydroxyarginine [5]. Valinophos is a valine ester of the previously unknown phosphonate scaffold dihydroxypropylphosphonic acid (DHPPA) [5, 7]. The phosphonoalamides are peptidic phosphonates containing the non- canonical amino acid phosphonalanine [8]. Produced by both Streptomyces spp. and Bacillus spp., phosphonoalamides exhibit broad spectrum antimicrobial activity against important human and plant pathogens [8,9]. Pantaphos, a hydroxylated and dehydrated analog of phosphonomethylmalate produced by the plant pathogen Pantoea ananatis, was shown to be necessary and sufficient in generating the hallmark lesions of onion center rot, but also shows potential to be developed as an herbicide

[0010] . The majority of known phosphonates have been isolated from terrestrial organisms, with fewer studies investigating phosphonate metabolism in marine environments. This is surprising, as marine natural products (NPs) are known to hold immense therapeutic potential [11, 12]. Reported biological activities for marine natural products are diverse, but cytotoxicity predominates

[0013] . While the ecological basis for this phenomonenon is unclear, these compounds have a proven track record in anticancer and analgesic drug development. Cytarabine was the first Food and Drug Administration (FDA) approved marine natural product (1969), indicated for various types of leukemias

[0014] . Since then, a handful of marine natural products have been brought to market, including Prialt (2004) for pain control, trabectedin (2007) for soft tissue sarcomas, eribulin (2010) for metastatic breast cancer, and brentuximab vedotin (2017) for both Hodgkin and non-Hodgkin lymphomas

[0014] . In addition to approved agents, numerous marine natural products are currently undergoing phase I-III clinical trials for cancer and pain management

[0015] . These successes are promising, but do not fully encapsulate the chemical diversity and potential applications of marine natural products. Phosphonate metabolism of surface ocean microbes has been surveyed, with approximately 15% of bacterioplankton encoding pepM

[0016] . However, genomic and chemical data suggest that the majority of these phosphonates are incorporated into cell surface phosphonoglycoproteins, which act to mitigate mortality caused by viral lysis and / or protozoan grazing

[0016] . The archaeon Nitrosopumilus maritimus was shown to produce methylphosphonate, which can be hydrolyzed by P-starved microbes in the upper ocean to release methane, explaining the marine methane paradox

[0017] . Phosphonates have also been isolated from higher organisms, including oysters (2-aminoethylphosphonate (2AEPn) from Crassostrea gigas) and sponges (phosphoiodyn from Placospongia sp.) [18, 19]. While 2AEPn is known to be incorporated into cell membrane phosphonolipids and phosphonoglycans, phosphoiodyn is the only phosphonate isolated from a marine organism with a reported biological activity. This compound was shown to be a potent agonist of human peroxisome proliferator activated receptor delta (PPAR-δ), a target in the treatment of metabolic disorders such as obesity and diabetes

[0020] . These studies address the phosphonate biosynthetic potential of planktonic marine bacteria and higher organisms, but those microbes found in marine sediment have been less well explored. As soil dwelling microbes produce almost all known members of this chemical class, the question asked was, are microbes in marine sediment capable of producing small molecule phosphonate natural products? This niche includes actinobacteria, which are prolific producers of bioactive natural products, accounting for approximately two-thirds of all antibiotics in clinical use today

[0021] . Phosphonate metabolism of terrestrial actinobacteria has been studied extensively. Indeed, most known phosphonates are produced by members of this genus, and studies of their biosyntheses have revealed countless unusual biochemical transformations, providing a roadmap to genome mine in the search for new compounds. Upon a survey of actinobacterial genomes, a phosphonate biosynthetic gene cluster encoded by the marine actinomycete Salinispora pacifica was detected. Heterologous expression of this biosynthetic gene cluster enabled isolation of a new a series of antimicrobial phosphonopeptides, of which one contains the non-canonical amino acid dehydromethylaspartate (DHMA). Compounds 1 and 2 were shown to inhibit both human and agricultural pathogens. These findings expand knowledge of phosphonate metabolism in marine microbes, marking the first small molecule phosphonate natural product to be isolated from a marine actinobacterium. Further, discovery of the non-canonical amino acid DHMA highlights the importance of investigating underexplored ecological niches in phosphonate discovery efforts. Results and Discussion Phosphonate Production and Purification. Streptomyces albus J1074 phiC31 attB::pKSJ452 was revived onto mannitol soy (MS) agar containing 25 µg / mL apramycin and incubated at 30 °C. A single colony was used to inoculate 5 mL of ATCC 172 in a 16 x 150 mm test tube, which was incubated at 30 °C for 3 days on a roller drum (80 RPM). This culture was used to inoculate 100 mL of ATCC 172 in a 500 mL baffled flask, which was incubated at 30 °C 200 rpm for 5 days on an incubator shaker. R2AS agar plates (20 L) and trays (8 L) were inoculated with 5 mL and 200 µL of the previous culture, respectively. Agar cultures were incubated at 30 °C for 10 days, frozen at -20 °C, thawed, and compressed to obtain a crude extract. Spent agar was submerged in methanol overnight to extract residual metabolites. An eleven-step procedure utilizing differential precipitation, batch sorption, size exclusion chromatography, solid-phase extraction, as well as normal and reverse-phase high- performance liquid chromatography (HPLC) was used to purify four phosphonates to homogeneity (Figure 1). The crude and methanolic extracts were concentrated to 700 mL under vacuum. Methanol was added to a final concentration of 70% and the sample incubated at -20 °C to precipitate unwanted insoluble components. Insoluble material was removed by centrifugation (8,000 rpm, 10 minutes, -20 °C). Methanol was removed by rotary evaporation and the sample concentrated to 400 mL. A second methanol precipitation (90%) was performed. Supernatant was harvested and concentrated (175 mL) as above. Precipitant was suspended in 100% methanol to extract residual methanol-soluble metabolites. The supernatant and methanol extract were combined, and concentrated by rotary evaporation, and diluted to 200 mL.200 g of Amberlite XAD16-N resin was added, and the sample was agitated overnight (80 rpm) in an incubator shaker (4 °C). Unbound material was recovered via filtration, then the resin was eluted with 3 L of dI H2O (250 mL fractions), followed by 500 mL of methanol. Loosely bound material (water fractions 1-9) was combined and concentrated by rotary evaporation to 50 mL, while the unbound material was concentrated to 150 mL. Both the XAD16-N unbound (150 mL) and loosely bound (50 mL) material were individually applied to a 3 L bed of Sephadex G-25 resin in a 5 x 150 cm column and eluted with dI H2O (10 mL / min-1). A total volume of 2.1 L were collected before collecting 100 mL fractions. Fractions containing phosphonates were pooled as follows; SP_A (1-7), SP_B (8-11), SP_C (12-13), SP_D (14-18). SP_B contained a putative phosphonopeptide based on NMR data. In the1H-31P HMBC spectrum, a phosphorous resonance (^P 17.85) showed correlations to two proton resonances (^H3.29 / 3.45 and 8.01), thought to be the methylene and amide protons of an aminomethylphosphonate residue involved in an amide bond ( Figure 12). This metabolite was targeted for further purification. SP_ C (25 mL) contained a small amount of the same compound. The sample was applied to a 1.25 L bed of Sephadex LH-20 resin in a 3.2 x 150 cm glass column and eluted with dI H2O (0.7 ml min-1). After an initial elution of 250 mL, 8 mL fractions were collected. phosphonate-containing fractions were pooled as follows; SP_C.1 (26- 55), SP_C.2 (56-74), SP_C.3 (75-99). Sample SP_B and SP_C.1 were combined, diluted four- fold and applied to a 200 mL bed of Oasis HLB resin in a 5 x 20 cm glass column that was previously equilibrated with 2 CV of 0.1% FA. The column was eluted with 200 mL volumes of the following solvents; 0.1% formic acid, 25% methanol, 50% methanol, and 100% methanol. All methanol fractions were combined and concentrated to 10 mL under vacuum, while the flow through (unbound metabolites) were kept separately. The HLB flow through (2 mL, 159 mg) was acidified to pH 3 with FA and applied to a 6 mL bed of Dowex 50WX8 conditioned with 0.1% formic acid. After collecting the unbound fraction, the column was eluted with 30 mL of dI H2O, collected as 3 mL fractions. Next, the column was eluted with 150 mL of 2% ammonium hydroxide, collected as 30 mL fractions. Water fractions were combined and lyophilized to yield aminomethylphosphonate. The first ammonium hydroxide fraction was lyophilized to yield partially purified 2- aminoethylphosphonate. The HLB-bound sample was successively separated (5 mL each time) over a 550 mL bed of BioGel P2 resin in a 2.5 x 120 cm glass column and eluted with dI H2O (0.5 mL min-1, 8 mL fractions). Upon separation, the putative phosphonopeptide observed in31P NMR spectra resolved into multiple compounds. Fractions containing phosphonates were pooled, dried under vacuum, and dissolved in 3 mL DI water. From this sample, 1 mL aliquots were successively applied to the same BioGel P2 column, 75 mL of eluent were collected, followed by 5 mL fractions. Fractions containing phosphonates (24-41) were pooled, dried under vacuum, and again dissolved in 5 mL of water. This sample (5 mL, 25 mg) was applied to a 150 mL bed of Oasis HLB resin in a 2.5 x 30 cm glass column. The column was connected to an Agilent 1260 Infinity II quaternary pump and eluted using the following gradient method; flow rate 0.1 mL min-1; 0-1500 min 100% solvent A (water 0.1% formic acid), 1500-4500 min linear gradient to 100% B (methanol 0.1% formic acid). Baseline resolution of distinct phosphonate species was observed.12 mL fractions were pooled based on the presence of like-signals in their31P NMR spectra; SP_1 (-), SP_2 (-), SP_3 (-), SP_4 (-). This column yielded 1.1 mg of pure compound 1 (SP_1), which was set aside for further chemical characterization. SP_3 was dried under vacuum (105 mg) and dissolved in 0.5 mL of water. This sample was applied to a 290 mL bed of BioGel P2 in a 1.5 x 170 cm column, eluting with water (0.2 mL min-1). A 40 mL volume was collected before collecting 4 ml fractions. Fractions 30-34 were pooled, dried under vacuum (29 mg), dissolved in 0.25 mL of water, and applied to a 95 mL bed of Sephadex LH20 in a 1 x 120 cm glass column. The column was eluted with water (0.2 mL min-1). Fractions 22-23 were pooled, dried under vacuum 5 mg, and dissolved in 0.5 mL of 50% aqueous acetonitrile. This sample was injected onto a Waters Xbridge amide column (10 x 250 mm, x µm) and eluted using the following method; flow rate 4 mL min-1; 0-5 minutes 80% solvent B (90:10 acetonitrile:water 10 mM ammonium bicarbonate), 5-7.5 minutes linear gradient to 25% solvent A (water 10 mM ammonium bicarbonate), 7.5-17.5 isochratic hold at 25% solvent A, 17.5-20 linear gradient to 60% solvent A, collecting 4 mL fractions. Fraction 11 was dried under vacuum (2 mg), dissolved in 20 µl of water, and injected onto a Phenomenex FusionRP column (4.6 x 250 mm, 4 µm) at a flow rate of 1.5 mL min-1. The column was eluted using the following gradient; 0-3 minutes 100% solvent A (water 10 mM ammonium bicarbonate), 3-15 minutes linear gradient to 100% solvent B (methanol 10 mM ammonium bicarbonate), collecting 0.75 mL fractions. This column yielded 0.8 mg of pure compound 2 (SP_2), and a 0.6 mg mixture of compounds 2 and 3 in an approximate 1:1 ratio. The mixture of compounds 2 and 3 was lyophilized, dissolved in 20 µL water, and injected onto a Phenomenex FusionRP column (4.6 x 250 mm, 4 µm) at a flow rate of 0.75 mL min-1. The column was eluted using the following gradient; 0-6 minutes 100% solvent A (water 0.1% formic acid), 6-30 minutes linear gradient to 100% solvent B (methanol 0.1% formic acid), collecting 0.5 mL fractions. Fraction 23 contained 0.1 mg of pure compound 3 (SP_3). Structure Elucidation of Isolated phosphonates Structure Elucidation of Aminomethylphosphonate. Aminomethylphosphonate (AmPn) was obtained as a white amorphous solid (Figure 2). Its molecular formula was deduced as CH7NO3P+ ([M+H]+calcd. m / z 112.0158, observed m / z 112.0155, Δppm = -2.6; Figure 52). AmPn was dissolved in 90% H2O 10% D2O for NMR experiments. One signal was present in the1H NMR spectrum (H-1; δH2.98, Figure 53), as well as in the31P NMR spectrum (P-a; δP10.81, Figure 54). Further, these two signals are correlated in the1H-31P HMBC spectrum ( Figure 55). All NMR and MS data are identical to reported literature values as well as an authentic aminomethylphosphonate standard [22, 23]. Structure Elucidation of Compound 1. Compound 1 was obtained as a white amorphous solid. Its molecular formula was deduced as C17H33N7O8P+from HRMS analysis ([M+H]+calcd. m / z 494.2123, observed m / z 494.2126, Δppm = 0.6 Figure 26). Compound 1 was dissolved in D2O for NMR experiments. Seventeen distinct signals were present in the13C NMR spectrum ( Figure 9, Table 1). The1H NMR spectrum showed 10 resonances due to the presence of 2 methyl groups (δH 0.88), 5 methylene groups (δH 3.39, 1.74 / 1.83, 1.56, 3.16, 5.94 / 6.34), and 4 methine groups (δH4.31, 4.10, 2.03, 4.86) ( Figure 7, Table 1). This was confirmed by multiplicity edited1H-13C HSQC and13C DEPT 135 data ( Figure 15, Figure 10). When the compound was dissolved in DMSO-d60.05% TFA, 4 additional resonances appeared in the1H NMR spectrum (δH8.01, 8.06, 8.30, 8.34) ( Figure 8, Table 2). These were shown to be from exchangeable amide and amine protons through1H-15N HSQC and1H-15N HMBC experiments ( Figure 17- Figure 18, Table 2), with the same experiments being used to determine the shift of their respective nitrogen atoms (δN101.49, 120.04, 117.91, 40.59 ). The1H-coupled31P NMR spectrum showed a single resonance at 17.85 ppm (P-a) ( Figure 9). The J-coupling constant for this signal (triplet, J = 12.1 Hz) was indicative of direct bonding to a methylene group.1H-31P HMBC data ( Figure 10) confirmed a correlation between the phosphorous atom (P-a; ^P 17.85) and methylene protons (H-1; ^H3.30 / 3.43), with1H-13C HSQC data again confirming these signals to be from a secondary carbon (C-1; ^C 37.38). In the13C NMR spectrum ( Figure 9), the resonance from C-1 is split into a doublet (^C 37.38, JCP = 145.1 Hz), giving further support to the presence of a P-CH2bond. In the1H-1H COSY ( Figure 13) and1H-1H TOCSY ( Figure 14) data, the H-1 methylene protons are correlated to one of the exchangeable amide protons (H-b, ^H 8.01), with1H-15N HSQC data ( Figure 17) being used to determine the shift of the N atom (N-b; ^N108.72). Altogether these data support the presence of an aminomethylphosphonate residue (AmPn) with an additional substituent at N-b. The chemical shift of N-b (^N 108.72) is typical of a nitrogen within in an amide bond. This was further corroborated by1H-13C HMBC data. The H-1 protons of AmPn were correlated to a quaternary carbon (C-1’; ^C172.86) in the1H-13C HMBC spectrum ( Figure 16), consistent with the carboxylate group of an amino acid. The1H-13C HMBC spectrum ( Figure 16) also showed correlation of C-1’ with a putative alpha proton of an amino acid (H-2’; ^H 4.31). In the1H-1H TOCSY spectrum ( Figure 12), H-2’ was correlated to 3 sets of methylene protons (H-3’, H-4’, H-5’; ^H1.54 / 1.66, 1.46, 3.08) and 2 exchangeable secondary amine protons (H-6’, H-c; ^H7.46, 8.06). Multiplicity of these resonances was determined from1H-13C HSQC,13C DEPT 135, and1H-15N HSQC spectra ( Figure 8, Figure 13, Figure 15). H-2’ was indeed attached to tertiary carbon C-2’ (^C53.5), while H-3’, H-4’, and H-5’ were attached to secondary carbons C- 3’, C-4’, C-5’ (^C 28.31, 24.31, and 40.45, respectively). Furthermore, H-6’ and H-c were attached to secondary amine nitrogen atoms (N-6’, N-c; ^N 84.99 and 120.04, respectively). These chemical shifts matched literature values for the side chain of arginine in the chemically analogous phosphonopeptide argolaphos A [5, 23]. In the1H-1H COSY spectrum ( Figure 13), a correlation between H-5’ and H-6’ places the guanidino group of arginine at the end of its aliphatic side chain. This was further confirmed by the correlation between H-6’ and C-7’ in the1H-13C HMBC spectrum ( Figure 14). Finally, the correlation between H-2’ and H-c in the1H-1H COSY spectrum ( Figure 13) suggested connection at N-c. Based on these data, it was reasoned that additional substituents were attached to the substructure at N-c (e.g. R-NH-Arg-AmPn). NMR correlations linking AmPn-Arg to another substituent were absent, even though two additional spin systems are clearly present within1H-1H COSY ( Figure 13) and1H-1H TOCSY ( Figure 14) data. Their chemical structures were established characterizing the nature of the linkages H, C, and N linkages within each system. The1H NMR spectrum ( Figure 8) identified a methine proton within the region for alpha protons of amino acids (H-2’’; ^H4.24). COSY experiments demonstrated connectivity between H-2’’ and methine proton H-3’’ (^H 2.03), which was further correlated to two sets of methyl protons (H-4’’ / 5’’; ^H 0.88) ( Figure 13). The multiplicity of these signals was confirmed by data from1H-13C HSQC and13C DEPT 135 experiments ( Figure 8, Figure 13). H-2’’ and H-3’’ were bound to tertiary carbons (C-2’’, C-3’’; ^C 60.12, and 29.82, respectively) and that H-4’’ and H-5’’ were bound to primary carbons (C-4’’, C5’’; ^C17.95 ). The1H-13C HMBC spectrum ( Figure 14) shows a correlation between H-2’’ and a quaternary carbon (C-1’’; ^C 172.82). Further, the1H-15N HMBC spectrum shows a correlation between H-3’’ and a nitrogen atom (N-d; ^N 117.56). The1H-15N HSQC spectrum ( Figure 15) was used to assign the corresponding amide proton (H-d; ^H8.30). Collectively, these data indicated the presence of a valine residue with an additional substituent at N-d. The remaining NMR data showed this substituent to be a fourth amino acid residue. In the1H-13C HMBC spectrum ( Figure 14), H-2’’ was correlated to a quaternary carbon (C-1’’’; ^C 168.52), which is likely from the carboxylate group of this amino acid residue bound to the nitrogen of valine via an amide bond. In the same spectrum, C-1’’’ was correlated to a methine group (H-2’’’; ^H 4.86). In the1H-1H COSY spectrum ( Figure 13), H-2’’’ has only one correlation to exchangeable amine protons (H-e; ^N8.34), with1H-15N HSQC data being used to confirm the shift of the amine nitrogen at the N-terminus of the putative peptide (N-e; ^N 40.59). In the1H-13C HMBC spectrum ( Figure 14), H-2’’’ was correlated to another quaternary carbon with a chemical shift typical of alkenes (C-3’’’; ^C137.23). Indeed, C-3’’’ correlated with two distinct proton resonances with chemical shifts consistent with an alkene moiety (H-4’’’; ^H 5.93 / 6.34). Each signal integrated to a normalized value of 1 proton, and were correlated to the same carbon in1H-13C HSQC data (C-4’’’; ^C130.19) ( Figure 8). These data demonstrate a terminal alkene residue is attached to C-3’’’. In the1H-13C HMBC spectrum ( Figure 14), H-2’’’ and H-4’’’ are correlated to an additional quaternary carbon (C-5’’’; ^C 170.8), which could only be directly bound to C-3’’’. The chemical shift of C-5’’’ suggests the presence of a terminal carboxylate group on the amino acid side chain. Collectively, these data suggest a new amino acid, which is named dehydromethylaspartate (DHMA). The NMR data elucidated two dipeptide substructures, Arg-AmPn and DHMA-Val. Thus, LC-MS / MS analyses were performed to establish the complete structure of compound 1 ( Figure 6, Table 4) . A fragment ion was observed for [AmPn-Arg-Val+H]+(fragment A calcd. m / z 367.1853, observed m / z 367.1843, Δ ppm = -2.8). This was also observed in fragmentation of the chemically analogous phosphonopeptide argolaphos A

[0023] . Other key fragments included [AmPn-Arg+H]+(fragment D calcd. m / z 251.0904, observed m / z 251.0904, Δppm = -2.8), [Val- DMA+H]+(fragment A calcd. m / z 199.1077, observed m / z 199.1073, Δppm = -2.0), [Arg-Val- DMA-H]+(fragment B calcd. m / z 383.2037, observed m / z 383.2028, Δppm = -2.3). From these data compound 1 was conclusively determined as a peptide with the following amino acid sequence, AmPn-Arg-Val-DMA. All NMR data, including1H,13C,13C DEPT135,31P,1H-31P HMBC,1H-13C HSQC,1H-13C HMBC,1H-1H COSY, and1H-1H TOCSY spectra were consistent with this structure ( Figure 7- Figure 17; Table 1- Table 2 and Table 3). The absolute configuration of valine and arginine were determined to be L by Marfey’s analysis ( Figure 59- Figure 60). This compound was named salinisporaphos A (Figure 2). Table 1.1H (700 MHz),13C (176 MHz), and15N (71 MHz) NMR data for compound 1 in D2O. Table 2.1H (700 MHz),31P (242 MHz), and15N (71 MHz) NMR data for compound 1 in DMSO-d6 with 0.05% TFA. Table 3. Summary of observed 2D NMR correlations.

[0002] Table 4. Key MS / MS fragments observed for compounds 1, 2, and 3. Structure Elucidation of Compound 2. Compound 2 was obtained as a white amorphous solid. Its molecular formula was deduced as C14H29N6O7P+from HRMS analysis ([M+H]+calcd m / z 425.1908, observed m / z 425.1893, Δppm = -3.5; Figure 19). Compound 2 was dissolved in D2O for NMR experiments. Fourteen distinct signals were observed in the13C NMR spectrum ( Figure 22, Table 5). The1H NMR spectrum ( Figure 21) showed 9 resonances from 3 methyl groups (^H0.89, 1.98), 4 methylene groups (^H3.20 / 3.37, 1.75 / 1.83, 1.71, 3.55), and 3 methine groups (^H 4.35, 4.03, 1.98) ( Figure 21, Table 5). These were confirmed by1H-13C HSQC and13C DEPT 135 experiments ( Figure 23, Figure 28). As with compound 1,1H,31P,13C,1H-31P HMBC,1H-13C HSQC, and1H-13C HMBC data ( Figure 21, Figure 24, Figure 22, Figure 25, Figure 28, and Figure 29, Table 5) indicate compound 2 contains an aminomethylphosphonate residue with an additional substituent at N-b. The1H-13C HMBC spectrum ( Figure 16) showed a correlation between H-1 and a quaternary carbon (C-1’; ^C 172.76), consistent with a carboxylate group from an amino acid residue. In the same spectrum, C-1’ correlated to a putative amino acid alpha proton (H-2’; ^H 4.35). As with compound 1, a spin system analogous to that of arginine were present within the1H-1H COSY (Figure 26) and1H-1H TOCSY (Figure 27) data, although with one subtle difference. The terminal methylene group of the arginine side chain was shifted slightly downfield (H-5’; ^H 3.50). This was previously observed in the arginine-containing phosphonopeptide argolaphos A where the Neposition of the arginine residue is hydroxylated

[0022] . These data indicate compound 2 contains an Ne-hydroxyarginine residue bound to aminomethylphosphonate via an amide bond. As with compound 1, a spin system analogous to that of valine is present within the1H-1H COSY ( Figure 26) and1H-1H TOCSY ( Figure 27) data, but correlations linking this spin system to the remainder of the molecule are absent from the NMR dataset. Furthermore, one resonance in the1H NMR spectrum remained unassigned (H-2’’’; ^H1.98). The1H-13C HSQC spectrum ( Figure 28) demonstrated H-2’’’ is bound to a primary carbon (C-2’’’; ^C21.56).The1H-13C HMBC ( Figure 16) revealed correlation between H-2’’’ and a quaternary carbon (C-1’’’; ^C 174.39). These data suggested this isolated spin as an acetyl group bound to the nitrogen of valine via an amide bond, but direct NMR correlations linking these two residues were not apparent. LC-MS / MS analyses were performed to determine the complete structure of compound 2 ( Figure 6, Table 4). This revealed several key fragments, including [AmPn-Arg+H]+(fragment E; calcd m / z 267.0853, observed m / z 267.0846, Δ ppm = -2.6), which is shared with compound 1. The diagnostic ion [Arg-Val-Ac+H]+(fragment G; calcd m / z 314.1823, observed m / z 314.1813, Δ ppm = -3.2) confirmed the connectivity of all residues in the peptide, with a subfragement [Val-Ac+H]+(fragment F; calcd m / z 114.0913, observed m / z 114.0911, Δ ppm = - 1.7) validating the N-acetylvaline group. From these data it was conclusively determined that compound 2 is a peptide with the following amino acid sequence, AmPn-Ne-hydroxyarginine- valine-Ac. The absolute configuration of valine and arginine were determined to be L by Marfey’s analysis ( Figure 61- Figure 62). Marfey’s analysis was performed using commercially available amino acid standards and a hydrolysate of argolaphos A isolated from Streptomyces monomycini. Notably, Ne-hydroxyarginine was unstable under acidic conditions and dehydrated to arginine in both compound 1 and argolaphos A. This molecule was named salinisporaphos B (Figure 2). Table 5.1H (700 MHz),13C (176 MHz), and31P (242 MHz) NMR data for compound 2 in D2O. Structure Elucidation of Compound 3. Compound 3 was obtained as a white amorphous solid. Its molecular formula was deduced as C14H30N6O6P+from HRMS analysis ([M+H]+calcd m / z 409.1959, observed m / z 409.1959, Δppm = 0.0, Figure 45, Table 8). Compound 3 was dissolved in D2O for NMR experiments. Due to limiting yield (0.1 mg) and the inherently low sensitivity of13C NMR experiments, a13C NMR spectrum was not acquired. Instead, all13C NMR shifts were assigned using a combination of1H-13C HSQC data ( Figure 51) and a separate NMR dataset acquired on an equimolar mixture of compounds 2 and 3 ( Figure 30- Figure 44, Table 6- Table 7). The1H NMR spectrum ( Figure 47) shows 9 distinct resonances from 3 methyl groups (^H0.87, 1.96), 4 methylene groups (^H3.15 / 3.31, 1.71 / 1.81, 1.58, 3.31), and 3 methine groups (^H 4.32, 4.00, 1.97). These signals were further confirmed by multiplicity edited1H-13C HSQC data ( Figure 51). Given low sample concentration, the31P NMR spectrum showed no resonances (data not shown), but the1H-31P HMBC spectrum ( Figure 48) showed correlations between a phosphorous atom (P-a; ^P13.8) and a set of methylene protons (H-1; ^H3.15 / 3.31). These correlations, similar to those observed in aminomethylphosphonate, compound 1, and compound 2, suggested that compound 3 also contains an aminomethylphosphonate residue with an additional substituent attached at N-b. As with compound 1, spin systems analogous to those of arginine and valine are present within the1H-1H COSY ( Figure 49) and1H-1H TOCSY ( Figure 50) data. The terminal methylene group of the arginine side chain (H-5’; ^H3.13) is shifted upfield compared to the cognate position in compound 2, indicating the presence of a canonical arginine residue rather than an Ne-hydroxyarginine ( Figure 47). An unassigned methyl group (H-2’’’; ^H 1.96), with multiplicity confirmed through1H-13C HSQC data (C-2’’’, ^C21.61) ( Figure 51), was reminiscent of the N-terminal acyl group present in compound 2. As with compounds 1 and 2, LC-MS / MS analyses were necessary to determine the complete structure of compound 3 ( Figure 46, Table 4). Several key fragments were identified, including [AmPn-Arg+H]+(fragment D; calcd m / z 251.0904, observed m / z 251.0898, Δ ppm = - 2.4). The diagnostic fragment [Arg-Val-Ac+H]+(fragment E; calcd m / z 298.1874, observed m / z 298.1868, Δ ppm = -2.0), was used to determine the order of the final two residues of the peptide, with the subfragment [Val-Ac+H]+(fragment F; calcd m / z 114.0913, observed m / z 114.0912, Δ ppm = -0.8) being used to establish the presence of an N-terminal acetylvaline moiety. From these data it was conclusively determined that compound 3 is a peptide with the following amino acid sequence, AmPn-Arg-Val-Ac. Due to limiting yield, Marfey’s analysis was not performed on compound 3. This compound was named salinisporaphos C (Figure 2). Table 6.1H (700 MHz),13C (176 MHz), and31P (242 MHz) NMR data for compound 2 and 3 mixture in DMSO-d6 with 0.05% TFA. Table 7.1H (700 MHz),13C (176 MHz), and31P (242 MHz) NMR data for compound 2 and 3 mixture in DMSO-d6 with 0.05% TFA. Table 8.1H (700 MHz),13C (176 MHz), and31P (242 MHz) NMR data for pure compound 3 in D2O. Chemospecific Reduction and Derivitization of Compound 1. Given the unprecedented nature of dehydromethylaspartate, chemispecific reduction and derivatization experiments were performed to further validate the presence of the terminal alkene moiety. An extract of S. Streptomyces albus J1074 phiC31 attB:pKSJ452 was treated with the reductant tris(2- carboxyethyl)phosphine (TCEP) and subsequently analyzed by LC-HRMS. Indeed, a reduced form of compound 1 was observed, in which dehydromethylaspartate was transformed to 3- methylaspartate ( Figure 67). Analysis by tandem MS identified key fragments of compound 1 containing 3-methylaspartate in lieu of dehydromethylaspartate ( Figure 68). To confirm this result, a 0.2 mg aliquot of compound 1 was dissolved in 6 N HCl and incubated at 100 °C overnight. The resultant hydrolysate was also subjected to treatment with TCEP and analyzed by LC-HRMS. Indeed, free 3-methylaspartate was now observed consistent with successful reduction of the terminal alkene by TCEP ( Figure 69). Given the electrophilic nature of the terminal alkene moiety of dehydromethylaspartate, it was hypothesized that treatment with a nucleophile would result in the formation of an adduct. An extract of Streptomyces albus J1074 phiC31 attB:pKSJ452 was treated with the mercaptan thioglycolic acid and analyzed by LC-HRMS. Indeed, a thioglycolate adduct of compound 1 (m / z 586.2055) was observed by LC-MS ( Figure 70). Analysis by tandem MS revealed a dehydrated fragment (m / z 568.1946) of derivatized compound 1 ( Figure 71). To further confirm this result, compound 1 hydrolysate was treated with thioglycolate in the same manner. Analysis by LC-HRMS revealed a thioglycolate adduct of free 3-methylaspartate (Figure 3). Tandem MS of the same sample revealed a key carbonyl sulfide fragment (m / z 178.0168), indicating successful derivatization of free dehydromethylaspartate (Figure 3). Altogether, these data conclusively demonstrate that compound 1 contains an N-terminal dehydromethylaspartate residue. Antimicrobial Activity. The antimicrobial activity of compounds 1-3 were determined against select bacteria and yeast using microbroth dilution assays ( Table 9). Compound 1 was shown to inhibit several strains of enterobacteria with varying potency. Escherichia coli WM6242, encoding an IPTG inducible phosphonate uptake system, was inhibited at 25 µM. Interestingly, the MIC was not decreased upon the addition of IPTG (100 µM). Serratia marcescens and Pantoea annanatis were also inhibited at 25 µM and 100 µM, respectively. Compound 2 was also shown to inhibit E. coli WM6242, but only upon the addition of IPTG (100 µM), demonstrating the expression of phosphonate uptake transporters is required for antimicrobial activity. Compound 3 was inactive against all assayed bacteria. None of the isolated compounds showed activity against the Gram positive bacteria assayed (Bacillus subtilis and Staphylococcus aureus). None of the compounds inhibited Saccharomyces cerevisiae. Table 9. Antibacterial activities of salinisporaphos A-C and synthetic aminomethylphosphonate. “-“ = not determined Discussion. Compounds 1-3, produced by a biosynthetic gene cluster from Salinispora pacifica, are the first small molecule phosphonate natural products reported from a marine actinobacterium. Their discovery adds to an already impressive repertoire of compounds produced by Salinispora spp

[0024] . Most notably, salinisporamide A is a potent proteasome inhibitor which has undergone numerous clinical trials for both solid tumors and hematologic malignancies

[0025] . Indeed, actinobacteria are storied producers of pharmaceutically relevant molecules, including most known phosphonates. While the phosphonate metabolism of terrestrial actinobacteria have been studied extensively, marine environments remain an underexplored ecological niche. This is notable, as evolutionary adaptations to highly variable marine environments have likely diversified phosphonate biosynthetic pathways within this taxon

[0026] . In searching for novel phosphonate inhibitors, marine actinobacteria may offer an untapped source of chemodiversity. This concept was demonstrated in the structure of compound 1, an unusual antimicrobial tetrapeptide containing three non-canonical amino acids: dehydromethylaspartate, Ne- hydroxyarginine, and aminomethylphosphonate (Gly-P). The salinisporaphos biosynthetic gene cluster is highly homologous to the argolophos phosphonopeptides produced by Streptomyces monomycini (Figure 4)

[0023] . In addition to the genes necessary for argolaphos biosynthesis, the S. pacifica biosynthetic gene cluster encodes uncharacterized genes which may contribute to formation of compound 1. These include a putative methylaspartate mutase and an ATP-grasp family enzyme ( Table 10). Methylaspartate mutase catalyzes isomerization of glutamate into the non-canonical amino acid 3-methylasapartate

[0027] . This residue is present in the natural products streptolydigin (Streptomyces lydicus) and friulimicin (Actinopanes friuliensis) [28, 29]. Both of these biosynthetic gene clusters encode experimentally characterized methylaspartate mutases, which share significant sequence similarity to that of S. pacifica, leading it to be hypothesized that this enzyme may supply 3-methylaspartate as a precursor in the biosynthesis of compound 1. ATP-grasp family enzymes have been shown to play a role in phosphonopeptide biosynthesis [7, 30]. The ATP-grasp encoded by the putative salinisporaphos cluster may be responsible for tetrapeptide formation. Dehydratases have been shown generate dehydrated amino acids elsewhere in Nature, but are not observed within the salinisporaphos cluster, indicating the alkene moiety of DHMA may generated by a unique mechanism. This tailoring step could happen before or after ligation to the nascent peptide chain

[0031] . Table 10. Annotation of proteins encoded by the putative Salinispora pacifica phosphonate biosynthetic gene cluster. Salinisporaphos is the first report of DHMA. Other dehydrated amino acids have been observed in natural products including ribosomally synthesized post-translationally modified peptides (RiPPs), non-ribosomal peptides (NRPs), and phosphonates. Nisin, a RiPP, contains both dehydroalanine and dehydrobutyrine

[0032] . Microcystins, NRP toxins produced by cyanobacteria, may contain one or both of these dehydrated residues [33, 34]. Didehydrohistidine, formed by a radical S-adenosylmethionine enzyme, was recently discovered within a RiPP produced by Streptococcus pneumoniae

[0035] . Further, an unusual phosphonate analog of dehydroalanine is observed in the peptide dehydrophos

[0036] . Each of these dehydrated residues are known to be part of the pharmacophore of their respective peptides [37-39]. E. coli WM6242 was inhibited by compounds 1 and 2 at different potencies (25 µM and 100 µM, respectively), which may be explained by differences in their chemical composition. The N-terminal residue of compound 1 is dehydromethylaspartate, while the N-terminus of compound 2 is acetylated. N-acetlyation is a common mechanism of detoxification in microbial metabolism, which may explain the reduced potency of compound 2

[0040] . Further, 3- methylaspartate is known to be antimicrobial as a free amino acid, inhibiting de novo pyrimidine biosynthesis

[0041] . While the bioactivity of free DHMA is unknown, the four-fold increase in potency compared to compound 2 suggests this residue likely contributes to antimicrobial activity. The only chemical difference between compounds 2 and 3 is the presence of a hydroxyl group on the Neposition of arginine, but compound 3 was completely devoid of inhibitory activity. These data suggest Ne-hydroxyarginine is an essential component of the pharmacophore. Indeed, Ne-hydroxyarginine is antimicrobial as a free amino acid, thought to be an inhibitor of glutamate acetyltransferase, which catalyzes the first step in arginine biosynthesis from glutamate

[0042] . Bioactivity of free aminomethylphosphonate was also evaluated alongside the isolated phosphonopeptides. Even at the highest concentration tested (1 mM), AmPn did not fully inhibit E. coli WM6242. Induction of phosphonate uptake transporters via the addition of IPTG (100 µM) shifted the MIC of AmPn to 3.90 µM, indicating this compound is a potent inhibitor, but not capable of penetrating the cell envelope by alternative mechanisms. Numerous phosphonopeptides hypothesized to act by a Trojan Horse type mechanism, where cellular uptake is facilitated by oligopeptide permeases, and cleavage by intracellular proteases releases the active phosphonate warhead [39, 43, 44]. This is likely true for AmPn containing peptides, including those isolated in this study. The potency of compound 1 was unaffected by the addition of IPTG, indicating this tetrapeptide is able to naturally transverse the cell envelope. Conversely, compound 2 was inactive against E. coli WM6242 without IPTG induction, indicating phosphonate transport was required for cellular uptake of the acetylated tripeptide. Compound 1 was also inhibited Serratia marcescens and Pantoea annanatis. S. marcescens is an opportunistic human pathogen, while P. annanatis causes disease in numerous cash crops

[0045] . Notably, none of the isolated compounds were active against Gram-positive bacteria. Selectivity for Gram-negative bacteria is an interesting trait, as the outer membrane acts as an additional barrier from the uptake of toxic molecules

[0046] . Indeed, Gram-negative pathogens are the primary cause of nosocomial infections, and are becoming increasingly resistant to available antibiotics

[0047] . While further studies will be needed to elucidate the molecular target(s) of compounds 1 and 2, perhaps they are absent from Gram-positives, or whether a lack of cellular uptake results in diminished activity. The discovery of compounds 1-3 expands the knowledge of phosphonate metabolism in marine microbes. Discovery of this non-canonical amino acid is a testament to the biosynthetic capabilities of marine actinobacteria, and highlights the importance of investigating underexplored environmental niches in phosphonate discovery efforts. Materials and Methods Chemicals and Reagents. All chemicals and reagents were from Sigma-Aldrich, Fisher Scientific, or VWR unless otherwise indicated. Media and General Culture Conditions. Media used in this study include: Mannitol soy agar (20 g mannitol, 20 g soy flour), ATCC 172 (10 g glucose, 20 g soluble starch, 5 g yeast extract, 5 g N-Z amine type A, 1 g CaCO3), R2A supplemented with succinate, LB (10 g tryptone, 10 g NaCl, 5 g yeast extract), YPD (10 g yeast extract, 20 g peptone, 20 g dextrose), Neidhart’s minimal medium

[0048] , YMM (6.7 g yeast nitrogen base without amino acids, 20 g dextrose). Neidhart’s minimal medium was supplemented with 1% casamino acids and 1 mM thiamine for growth of Staphyloccous. All components were dissolved in deionized water (dI H2O).16 g of agar were added per liter of media. Escherichia, Pseudomonas, Salmonella, and Staphylococcus strains were grown at 37 °C. All others strains were grown at 30 °C. Bioinformatics. Sequences encoding putative biosynthetic gene clusters were retrieved from NCBI. Open reading frames and synteny were analyzed using EasyFig, clinker, and cblaster [49-51]. BLAST analyses were performed against the NCBI non-redundant (nr) protein database and Pfam

[0052] . NMR and Mass Spectrometry. All NMR and MS data were analyzed using MestReNova software.1H,13C, and15N NMR spectra were acquired at 25 °C in either 10% D2O or DMSO-d6 on a Bruker Avance III HD 700 MHz spectrometer equipped with a triple resonance cryoprobe.31P NMR spectra were recorded on a Bruker Avance III HD 600 MHz spectrometer equipped with a 5 mm Smart Broadband Probe or a Bruker Avance NEO 400 MHz spectrometer equipped with a triple resonance cryoprobe. Mass spectra were acquired on a Thermo Q-Exactive Orbitrap with a Vanquish-H UHPLC using a Thermo Accucore RP-MS column (compound 1) or a Waters BEH Amide column (compound 2, compound 3, AmPn, 2AEPn). The Accucore RP-MS column (2.1 x 50 mm, 2.6 µm) was eluted using the following method; flow rate 0.2 mL min-1; 0-2 minutes 98% solvent A (water 0.1% formic acid (FA)); 2-5 minutes linear gradient to 100% solvent B (MeCN 0.1% FA); 5-6 minutes 100% solvent B. The Waters BEH Amide column (2.1 x 150 mm, 4.6 µm) was eluted using the following method; flow rate 0.35 mL min-1; 0-2 minutes 85% solvent B (MeCN 0.1% formic acid); 2-6 minutes linear gradient to 40% solvent A (water 0.1% FA); 6-9 minutes 40% solvent A. For collection of MS / MS mode, the instrument was set to PRM mode with collision energy (CE) set at 35 eV. For HRMS analysis of extracts from the heterologous expression strain, samples were first treated by anion exchange chromatography using Fe-bound Chelex 100 resin. A 100 µl bed of resin was equilibrated with 0.1% FA, and 200 µl of sample (pH 3, formic acid) were applied. Anionic species were allowed to bind to the resin as the sample was gently mixed on a nutator for 10 minutes. The unbound sample was collected, and the resin eluted with 1 mL of 0.1% formic acid, followed by 1 mL of 500 mM ammonium bicarbonate (pH 7.8). The ammonium bicarbonate fraction was lyophilized, dissolved in 200 µl of water, and then diluted to 70% MeCN.10 µl was injected onto a Waters BEH Amide column (2.1 x 150 mm, 4.6 µm) and eluted using the same method as above. Chemical Data of Purified Compounds 1-aminomethylphosphonate: White powder;1H NMR (700 MHz, D2O, ^, ppm, J / Hz), 2.98 (2H, d, J = 12.80 Hz, H-1); ESI HRMS calc’d for CH7NO3P+: 112.0158, observed: 112.0155 (Δppm = -2.6). (1-aminomethylphosphonate)-arginylvalyldehydromethylaspartate (compound 1; Salinisporaphos A): White powder;1H NMR (700 MHz, D2O, ^, ppm, J / Hz), 3.39 (2H, d, J = 12.6 Hz, H-1), 4.31 (1H, dd, J = 8.9, 5.2 Hz, H-2’), 1.74 / 1.83 (2H, m, H-3’), 1.56 (2H, m, H-4’), 3.16 (2H, m, H-5’), 4.1 (1H, d, 7.3 Hz, H-2’’), 2.03 (1H, m, H-3’’), 0.88 (6H, t, J = 6.25 Hz, H- 4’’ / 5’’), 4.86 (1H, s, H-2’’’), 5.93 / 6.34 (2H, s, H-4’’’);13C NMR (176 MHz, D2O, ^, ppm, J / Hz), 37.38 (CH2, d, J = 145.1, C-1), 172.86 (qC, s, C-1’), 53.35 (CH, s, C-2’), 28.31 (CH2, s, C-3’), 24.31 (CH2, s, C-4’), 40.45 (CH2, s, C-5’), 156.79 (qC, s, C-7’), 172.82 (qC, s, C-1’’), 60.12 (CH, s, C-2’’), 29.82 (CH, s, C-3’’), 17.95 (CH, s, C-4’’ / 5’’), 168.52 (CH, s, C-1’’’), 55.10 (CH, s, C-2’’’), 137.23 (qC, s, C-3’’’), 130.19 (CH2, s, C-4’’’), 170.80 (qC, s, C-5’’’);31P NMR (162 MHz, DMSO, ^, ppm); 17.85 (P-CH2, t, JCP= 12.1 Hz, P-a); ESI HRMS calcd for C17H33N7O8P+: 494.2123, observed: 494.2126 (Δppm = -0.8). (1-aminomethylphosphonate)- Ne-hydroxyarginylacetylvaline (compound 2; Salinisporaphos B): White powder;1H NMR (700 MHz, D2O, ^, ppm, J / Hz), 3.20 / 3.37 (2H, m, H-1), 4.35 (1H, t, J = 6.2 Hz), 1.75 / 1.83 (2H, m, H-3’), 1.21 (2H, m, H-4’), 3.55 (2H, t, J = 6.7 Hz, H-5’), 4.03 (2H, d, J = 7.5 Hz, H-2’’), 1.98 (1H, sept, J = 7.1 Hz, H-3’’), 0.89 (6H, t, J = 7.0, H-4’’ / 5’’), 1.98 (3H, s, H-2’’’);13C NMR (176 MHz, D2O, ^, ppm, J / Hz), 38.06 (CH2, d, J = 141.9 Hz, C-1), 172.76 (qC, s, C-1’), 53.35 (CH, s, C-2’), 28.17 (CH2, s, C-3’), 22.06 (CH2, s, C- 4’), 50.58 (CH2, s, C-5’), 157.65 (qC, s, C-7’), 173.79 (qC, s, C-1’’), 59.68 (CH, s, C-2’’), 29.96 (CH, s, C-3’’), 18.00 (CH3, s, C-4’’ / 5’’), 174.39 (qC, s, C-1’’’), 21.56 (CH3, s, C-2’’’);31P NMR (162 MHz, D2O, ^, ppm) 14.12 (P-CH2, s, P-a); ESI HRMS calcd for C14H29N6O7P+: 425.1908, observed: 425.1893 (Δppm = -3.5). (1-aminomethylphosphonate)-arginylacetylvaline (compound 3; Salinisporaphos C): White powder;1H NMR (700 MHz, D2O, ^, ppm, J / Hz), 3.15 / 3.31 (2H, m, H-1), 4.32 (1H, dd, J = 5.8, 2.55, H-2’), 1.71 / 1.81 (2H, m, H-3’), 1.58 (2H, m, H-4’), 3.13 (2H, m, H-5’), 4.00 (1H, d, J = 7.7 Hz, H-2’’), 1.97 (1H, m, H-3’’), 0.87 (6H, t, J = 7.13, H-4’’ / 5’’), 1.98 (3H, s, H-2’’’);13C NMR (176 MHz, D2O, ^, ppm, J / Hz), 53.25 (CH, s, C-2’), 28.32 (CH2, s, C-3’), 24.42 (CH2, s, C-4’), 40.17 (CH2, s, C-5’), 59.81 (CH, s, C-2’’), 29.95 (CH, s, C-3’’), 18.00 (CH3, s, C-4’’ / 5’’), 21.61 (CH3, s, C-2’’’);31P NMR (162 MHz, D2O, ^, ppm) 13.82 (P-CH2, s, P-a); ESI HRMS calcd for C14H29N6O7P+: 409.1959, observed: 409.1959 (Δppm = 0.0). Marfey’s analysis. Compounds 1 and 2 (0.2 mg) were dissolved in 0.5 mL of 6 N HCl and heated to 100°C in a sealed reaction vial for 16 h. Samples were dried at 40°C under a gentle stream of air to remove HCl. Hydrolysates were dissolved in 50 μL of water and transferred to microcentrifuge tubes, and 50 mM solutions (50 μL) of each amino acid standard were prepared. Each sample or standard was combined with 20 μL of 1 M NaHCO3 and 100 μL of a 1% solution of Nα-(2,4-Dinitro-5-fluorophenyl)-L-alaninamide (FDAA) in acetone and incubated in a heating block at 40°C for 1 h. Samples were cooled to room temperature and neutralized with 20 μL of 1 M HCl. Derivatized amino acid standards and hydrolysates were diluted 50-fold into 10% MeCN with 0.1% FA. Derivatized PnAla solutions were diluted 50-fold into water with 0.1% FA. These were analyzed by LC-MS using an Accucore RP-MS column (2.1 x 50 mm, 2.6 µm) eluted using the same method described previously or a Phenomenex Fusion-RP column (2 x 100 mm, 4 μm) eluted using the following method; flow rate 0.35 mL min-1; 0-1 min 100% solvent A (0.1% formic acid), 1-31 min linear gradient to 50% solvent B (MeCN 0.1% formic acid), 31-31.1 min linear gradient to 100% solvent B, 31.1-33 minutes min hold at 100% solvent B. Chemospecific reduction of the dehydromethylaspartate vinyl moiety. Extracts of Streptomyces albus J1074 phiC31 attB::pKSJ452 and Streptomyces albus J1074 phiC31 attB::pAE4 were treated with tris(2-carboxyethyl)phosphinehydrochloride (TCEP), a strong reducing agent, to transform the alkene moiety of dehydromethylaspartate to the corresponding alkane 3-methylaspartate. These reactions were buffered in Tris-Cl (500 µM, pH 8), with the final concentration of TCEP being 500 µM. Reactions were incubated at 37 °C for 24 hours, quenched with 5 µl of 1 M HCl, diluted to 70% MeCN, then analyzed by LC-HRMS and tandem MS on a Waters BEH amide column (4.6 x 150 mm, 4 µM) eluted using the previously described method ( Figure 67- Figure 68). 0.2 mg of compound 1 was dissolved in 6 N HCl and incubated at 100 °C in a sand bath overnight. A small aliquot of the hydrolysate, along with commercially available 3- methylaspartate (50 µM), were also treated with TCEP and analyzed as described above ( Figure 69). Chemospecific derivitization of the dehydromethylaspartate vinyl moiety. Previously prepared extracts of Streptomyces albus J1074 phiC31 attB::pKSJ452 and Streptomyces albus J1074 phiC31 attB::pAE4 were treated with sodium thioglycolate (TG), a nucleophilic mercaptan, to derivatize the alkene moiety of dehydromethylaspartate to the corresponding 3- methylaspartate thioether. These reactions were buffered in sodium acetate (50 µM, pH 3.8), with the final concentration of TG being 40 mM. Reactions were incubated at 25 °C for 24 hours, quenched with TFA (final concentration 0.3 %), diluted to 70% MeCN, then analyzed by LC-HRMS and tandem MS on a Waters BEH amide column (4.6 x 150 mm, 4 µM) eluted using the previously described method ( Figure 70- Figure 71). 0.2 mg of compound 1 was dissolved in 6 N HCl and incubated at 100 °C in a sand bath overnight. A small aliquot of the hydrolysate, along with commercially available 3- methylaspartate (50 µM), were also treated with TG and analyzed as described above ( Figure 72- Figure 73). Microbroth dilution assays . Compounds 1, 2, and 3 were repeatedly lyophilized and exchanged with ultrapure dIH2O until all residual modifier was removed prior to assays. Susceptibility testing was performed using the broth microdilution method in 96 round-well microtiter plates following general guidelines by the Clinical and Laboratory Standards Institute, but with the following modifications. Compounds were prepared as 50x stocks (10 mM) by dissolving in dIH2O. All bacterial strains were grown and assayed in Neidhart’s minimal medium (with amendments added as required). Yeast strains were grown and assayed in YMM. Controls wells contained kanamycin or fosfomycin (for bacteria) or nystatin (for yeasts), no compound addition (vehicle only), and no cell addition (media added instead). Culture densities (optical densities at 600 nm [OD600]) were recorded using a Bio-Rad xMark microplate spectrophotometer after 16 h for all strains except bacilli, which were recorded after 20 h. MIC was defined as the lowest concentration of compound that resulted in ≥90% growth inhibition. MIC values reflect triplicate assays performed on separate days. Table 11. Strains used in bioassays. Table 12. Summary of MIC90 values from microbroth dilution assays Fos = fosfomycin; Kan = kanamycin; Nys = nystatin References 1. Shoji JI et al. The Journal of antibiotics, 1986, 39, 1011-1012. 2. Bayer VE et al. Helvetica Chimica Acta, 1972, 55, 224-239. 3. Yamato M et al. The Journal of antibiotics, 1986, 39, 44-52. 4. Metcalf WW et al. Annu Rev Biochem, 2009, 78, 65-94. 5. Ju KS et al. Proc Natl Acad Sci U S A, 2015, 112, 12175-12180. 6. Kim J et al. Biochemistry, 1996, 35, 4628-4635. 7. Zhang Y et al. Journal of the American Chemical Society, 2022, 144, 9938-9948. 8. Kayrouz CM et al. ACS Chemical Biology, 2020, 15, 1921-1929. 9. Wilson J et al. Applied and Environmental Microbiology, 2023, e00338-00323. 10. Polidore ALA et al. Mbio, 2021, 12, e03402-03420. 11. Molinski TF et al. Nature reviews Drug discovery, 2009, 8, 69-85. 12. Jimenez C, ACS Med Chem Lett, 2018, 9, 959-961. 13. Hu Y et al. Marine drugs, 2015, 13, 202-221. 14. Jiménez C. 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Woolley DW et al. Journal of Biological Chemistry, 1960, 235, 3238-3241. 42. Maehr H et al. The Journal of antibiotics, 1973, 26, 284-288. 43. Kugler M et al. Arch Microbiol, 1990, 153, 276-281. 44. Abouhamad WN et al. Mol Microbiol, 1991, 5, 1035-1047. 45. Coutinho TA et al. Molecular plant pathology, 2009, 10, 325-335. 46. Imai Y et al. Nature, 2019, 576, 459-464. 47. Payne DJ et al. Nature reviews Drug discovery, 2007, 6, 29-40. 48. Neidhardt FC et al. Journal of bacteriology, 1974, 119, 736-747. 49. Sullivan MJ et al. Bioinformatics, 2011, 27, 1009-1010. 50. Gilchrist CLM et al. Bioinformatics, 2021, 37, 2473-2475. 51. Gilchrist CLM et al. Bioinformatics Advances, 2021, 1, vbab016. 52. Bateman A et al. Nucleic acids research, 2004, 32, D138-D141. EXEMPLARY ASPECTS In view of the described compositions, devices, systems, and methods, herein below are described certain more particularly described aspects of the inventions. The particularly recited aspects should not, however, be interpreted to have any limiting effect on any different claims containing different or more general teachings described herein or that the “particular” aspects are somehow limited in some way other than the inherent meanings of the language and formulas literally used therein. Example 1: A compound defined by Formula I: I wherein R1is hydrogen, halide, substituted or unsubstituted C1-C20 alkyl, substituted or unsubstituted C3-C20cycloalkyl, substituted or unsubstituted C1-C20alkoxy, substituted or unsubstituted C3-C20 aryl (e.g., substituted or unsubstituted phenyl), substituted or unsubstituted C4-C21 alkylaryl, NRxRy, or ORa; R2is hydrogen, halide, substituted or unsubstituted C1-C20alkyl, substituted or unsubstituted C3-C20cycloalkyl, substituted or unsubstituted C1-C20alkoxy, substituted or unsubstituted C3-C20 aryl (e.g., substituted or unsubstituted phenyl), substituted or unsubstituted C4-C21alkylaryl, NRxRy, or ORb; R3is hydrogen, hydroxyl, halide, substituted or unsubstituted C1-C20alkyl, substituted or unsubstituted C1-C20 acyl, substituted or unsubstituted C1-C20 alkoxy, substituted or unsubstituted C1-C20amide, NRxRy, or one or more amino acids (e.g., one or more canonical or non-canonical amino acids); Raand Rbare each independently hydrogen, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C3-C10aryl (e.g., substituted or unsubstituted phenyl), or substituted or unsubstituted C4-C11 alkylaryl; and Rxand Ryare independently selected from hydrogen, or substituted or unsubstituted C1- C5alkyl, or substituted or unsubstituted C1-C5acyl; or a derivative or salt thereof. Example 2: The compound of any example herein, particularly example 1, wherein R1is ORaand / or R2is ORb. Example 3: The compound of any example herein, particularly example 1 or example 2, wherein the compound is defined by Formula II: II wherein R3is hydrogen, hydroxyl, halide, substituted or unsubstituted C1-C20alkyl, substituted or unsubstituted C1-C20 acyl, substituted or unsubstituted C1-C20 alkoxy, substituted or unsubstituted C1-C20 amide, NRxRy, or one or more amino acids (e.g., one or more canonical or non-canonical amino acids); Raand Rbare each independently hydrogen, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C3-C10 aryl (e.g., substituted or unsubstituted phenyl), or substituted or unsubstituted C4-C11alkylaryl; and Rxand Ryare independently selected from hydrogen, or substituted or unsubstituted C1- C5 alkyl, or substituted or unsubstituted C1-C5 acyl; or a derivative or salt thereof. Example 4: The compound of any example herein, particularly examples 1-3, wherein Raand / or Rbis hydrogen. Example 5: The compound of any example herein, particularly examples 1-4, wherein the compound is defined by Formula III: III wherein R3is hydrogen, hydroxyl, halide, substituted or unsubstituted C1-C20alkyl, substituted or unsubstituted C1-C20 acyl, substituted or unsubstituted C1-C20 alkoxy, substituted or unsubstituted C1-C20amide, NRxRy, or one or more amino acids (e.g., one or more canonical or non-canonical amino acids); Rais hydrogen, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C3- C10 aryl (e.g., substituted or unsubstituted phenyl), or substituted or unsubstituted C4-C11 alkylaryl; and Rxand Ryare independently selected from hydrogen, or substituted or unsubstituted C1- C5 alkyl, or substituted or unsubstituted C1-C5 acyl; or a derivative or salt thereof. Example 6: The compound of any example herein, particularly examples 1-5, wherein the compound is defined by Formula IV: IV wherein R3is hydrogen, hydroxyl, halide, substituted or unsubstituted C1-C20alkyl, substituted or unsubstituted C1-C20 acyl, substituted or unsubstituted C1-C20 alkoxy, substituted or unsubstituted C1-C20 amide, NRxRy, or one or more amino acids (e.g., one or more canonical or non-canonical amino acids); and Rxand Ryare independently selected from hydrogen, or substituted or unsubstituted C1- C5 alkyl, or substituted or unsubstituted C1-C5 acyl; or a derivative or salt thereof. Example 7: The compound of any example herein, particularly examples 1-6, wherein R3is one or more amino acids (e.g., one or more canonical or non-canonical amino acids). Example 8: The compound of any example herein, particularly examples 1-7, wherein R3is one or more amino acids, each amino acid independently being selected from the group consisting of Arginine (Arg), Ne-hydroxyarginine, dehydro‐3‐methylaspartate, and Valine (Val). Example 9: The compound of any example herein, particularly examples 1-8, wherein the compound is defined by Formula V: wherein R4and R5are each independently hydrogen, hydroxyl, halide, substituted or unsubstituted C1-C20alkyl, substituted or unsubstituted C1-C20acyl, substituted or unsubstituted C1-C20alkoxy, substituted or unsubstituted C1-C20 amide, NRxRy, or one or more amino acids (e.g., one or more canonical or non-canonical amino acids); and Rxand Ryare independently selected from hydrogen, or substituted or unsubstituted C1- C5alkyl, or substituted or unsubstituted C1-C5acyl; or a derivative or salt thereof. Example 10: The compound of any example herein, particularly example 9, wherein R4and R5are each independently one or more amino acids (e.g., one or more canonical or non- canonical amino acids), or a derivative or salt thereof. Example 11: The compound of any example herein, particularly example 9 or example 10, wherein R4and R5are each independently one or more amino acids, each amino acid independently being selected from the group consisting of Arginine (Arg), Ne-hydroxyarginine, dehydro‐3‐methylaspartate, and Valine (Val), or a derivative or salt thereof. Example 12: The compound of any example herein, particularly examples 1-11, wherein the compound comprises AmPn-Arg-Val-DMA, AmPn-Ne-hydroxyarginine-Val-Ac, AmPn- Arg-Val-Ac, a derivative or salt thereof, or a combination thereof. Example 13: The compound of any example herein, particularly examples 1-12, wherein the compound is selected from the group consisting of: , , or salts thereof, and combinations thereof. Example 14: The compound of any example herein, particularly examples 1-13, wherein the compound is selected from the group consisting of: , , or salts thereof, and combinations thereof. Example 15: The compound of any example herein, particularly examples 1-14, wherein the compound is selected from the group consisting of: , , atives or salts thereof, and combinations thereof. Example 16: The compound of any example herein, particularly examples 1-15, wherein the compound is selected from the group consisting of: , , derivatives or salts thereof, and combinations thereof. Example 17: The compound of any example herein, particularly examples 1-16, wherein the compound is a salt. Example 18: The compound of any example herein, particularly examples 1-17, wherein the compound is a salt form of Formula I, Formula II, Formula III, Formula IV, Formula V, or a combination thereof with a counterion. Example 19: The compound of any example herein, particularly examples 1-18, wherein the compound is a salt form of Formula II with a counterion. Example 20: The compound of any example herein, particularly examples 1-19, wherein the compound is a salt form of Formula II with a counterion and the salt form of the compound is selected from the group consisting of: and combinations thereof. Example 21: The compound of any example herein, particularly examples 18-20, wherein the counterion is a monovalent or divalent counterion. Example 22: The compound of any example herein, particularly examples 18-21, wherein the counterion is selected from the group consisting of sodium, potassium, calcium, lithium, magnesium, manganese, ammonium, iron, and combinations thereof. Example 23: The compound of any example herein, particularly examples 1-22, wherein the compound is a potassium salt, sodium salt, calcium salt, iron salt, ammonium salt, or a combination thereof. Example 24: The compound of any example herein, particularly examples 1-23, wherein the compound comprises an agriculturally acceptable salt thereof and / or a pharmaceutically acceptable salt thereof. Example 25: The compound of any example herein, particularly examples 1-24, wherein the compound is a tetra-peptide. Example 26: The compound of any example herein, particularly examples 1-25, wherein the compound is an isolate of a marine organism, or a derivative or salt thereof. Example 27: The compound of any example herein, particularly examples 1-26, wherein the compound is a Salinispora isolate or a derivative or salt thereof. Example 28: The compound of any example herein, particularly examples 1-27, wherein the compound is a Salinispora pacifica isolate or a derivative or salt thereof. Example 29: A composition comprising the compound of any example herein, particularly examples 1-28. Example 30: The composition of any example herein, particularly example 29, wherein the composition further comprises one or more agriculturally acceptable and / or pharmaceutically acceptable carriers. Example 31: The composition of any example herein, particularly example 29 or example 30, wherein the composition comprises a pharmaceutical composition, an agricultural composition, or a combination thereof. Example 32: The composition of any example herein, particularly examples 29-31, wherein the composition comprises a pesticide. Example 33: The composition of any example herein, particularly examples 29-32, wherein the composition comprises an herbicide. Example 34: The composition of any example herein, particularly examples 29-33, wherein the composition exhibits antimicrobial activity. Example 35: The composition of any example herein, particularly examples 29-34, wherein the composition results in at least 5 log reduction of a population of microbes. Example 36: The composition of any example herein, particularly example 35, wherein the microbes are one or more microorganisms selected from the group consisting of gram negative bacteria. Example 37: The composition of any example herein, particularly example 35 or example 36, wherein the microbes are one or more microorganisms selected from the group consisting of Escherichia coli, Serratia marcescens, and Pantoea ananatis. Example 38: The composition of any example herein, particularly examples 29-37, further comprising a solvent, a carrier, an excipient, or a combination thereof. Example 39: The composition of any example herein, particularly examples 29-38, further comprising an agriculturally acceptable adjuvant or carrier. Example 40: The composition of any example herein, particularly examples 29-39, wherein the composition is formulated for delivery to a plant or animal. Example 41: The composition of any example herein, particularly examples 29-40, wherein the composition is formulated for delivery to a plant. Example 42: The composition of any example herein, particularly example 41, wherein the plant comprises a crop. Example 43: The composition of any example herein, particularly example 41 or example 42, wherein the composition is formulated for delivery to onions. Example 44: The composition of any example herein, particularly examples 29-40, wherein the composition is formulated for delivery to an animal. Example 45: The composition of any example herein, particularly example 44, wherein the animal is a companion animal, livestock, research animal, insect, or human. Example 46: The composition of any example herein, particularly example 44 or example 45, wherein the animal is an insect. Example 47: The composition of any example herein, particularly example 46, wherein the insect is a bee, such as a honeybee. Example 48: A nucleic acid encoding the compound or composition of any example herein, particularly examples 1-47. Example 49: A vector encoding the nucleic acid of any example herein, particularly example 48. Example 50: A cell comprising the vector of any example herein, particularly example 49. Example 51: A cell comprising the compound or composition of any example herein, particularly examples 1-47. Example 52: The cell of any example herein, particularly example 50 or example 51, wherein the cell comprises a marine organism cell. Example 53: The cell of any example herein, particularly examples 50-52, wherein the cell comprises an actinobacterium cell. Example 54: The cell of any example herein, particularly examples 50-53, wherein the cell comprises a Salinispora cell. Example 55: The cell of any example herein, particularly examples 50-54, wherein the cell comprises a Salinispora pacifica cell. Example 56: A method of making the compound of any example herein, particularly examples 1-28. Example 57: The method of any example herein, particularly example 56, wherein the method is a biosynthetic method. Example 58: The method of any example herein, particularly example 56 or example 57, wherein the method uses one or more enzymes derived from Salinispora, such as Salinispora pacifica. Example 59: A method of use of the compound, composition, nucleic acid, vector, and / or cell of any example herein, particularly examples 1-55. Example 60: The method of any example herein, particularly example 59, wherein the method comprises using the compound, composition, nucleic acid, vector, and / or cell as an antimicrobial, herbicide, pesticide, or combination thereof to control an undesirable population. Example 61: The method of any example herein, particularly example 60, wherein the method comprises using the compound, composition, nucleic acid, vector, and / or cell as a pesticide. Example 62: The method of any example herein, particularly example 61, wherein the method comprises using the compound, composition, nucleic acid, vector, and / or cell to control an undesirable population in plants. Example 63: The method of any example herein, particularly example 62, wherein the method comprises contacting the plants or the locus thereof with or applying to the soil or water the compound, composition, nucleic acid, vector, and / or cell. Example 64: The method of any example herein, particularly examples 61-63, further comprising applying an additional pesticide. Example 65: The method of any example herein, particularly examples 60-64, wherein the undesirable population is an herbicide resistant or tolerant population, a pesticide resistant or tolerant population, an antimicrobial resistant or tolerant population, or a combination thereof. Example 66: The method of any example herein, particularly examples 60-65, wherein the undesirable population comprises bacteria. Example 67: A method of reducing the activity of bacteria, the method comprising exposing the bacteria to an effective amount of the compound, composition, nucleic acid, vector, and / or cell of any example herein, particularly examples 1-55. Example 68: A method of reducing bacterial population, the method comprising exposing the bacteria to an effective amount of the compound, composition, nucleic acid, vector, and / or cell of any example herein, particularly examples 1-55. Example 69: A method of killing bacteria, the method comprising exposing the bacteria to an effective amount of the compound, composition, nucleic acid, vector, and / or cell of any example herein, particularly examples 1-55. Example 70: A method for treating, preventing, inhibiting, and / or ameliorating a disease or disorder in a plant or a subject in need thereof, the method comprising administering to the plant or subject a therapeutically effective amount of the compound, composition, nucleic acid, vector, and / or cell of any example herein, particularly examples 1-55. Example 71: The method of any example herein, particularly example 70, wherein the disease or disorder comprises an infection, such as a microbial infection. Example 72: A method for treating, preventing, inhibiting, and / or ameliorating a microbial infection in a plant or a subject, comprising administering to the plant or subject an effective amount of the compound, composition, nucleic acid, vector, and / or cell of any example herein, particularly examples 1-55. Example 73: The method of any example herein, particularly example 71 or example 72, wherein the microbial infection comprises a bacterial infection. Example 74: The method of any example herein, particularly examples 66-73, wherein the bacteria comprise gram negative bacteria. Example 75: The method of any example herein, particularly examples 66-74, wherein the bacteria comprise one or more bacteria selected from the group consisting of Escherichia coli, Serratia marcescens, and Pantoea ananatis. Example 76: The method of any example herein, particularly examples 70-75, wherein the plant is a crop. Example 77: The method of any one of clams 70-76, wherein the plant is an onion. Example 78: The method of any example herein, particularly examples 70-75, wherein the subject is an animal. Example 79: The method of any example herein, particularly example 78, wherein the animal is a companion animal, livestock, research animal, insect, or human. Example 80: The method of any example herein, particularly example 78 or example 79, wherein the animal is an insect. Example 81: The method of any example herein, particularly example 80, wherein the insect is a bee, such as a honeybee. Example 82: The method of any example herein, particularly examples 60-81, wherein the compound, composition, nucleic acid, and / or vector is delivered via cultured Salinispora pacifica. Example 83: A method of isolating and / or purifying a compound produced by a cell, wherein the compound comprises the compound of any example herein, particularly examples 1- 28. Example 84: The method of any example herein, particularly example 83, wherein the cell comprises a marine organism cell. Example 85: The method of any example herein, particularly examples 83-84, wherein the cell comprises an actinobacterium cell. Example 86: The method of any example herein, particularly examples 83-85, wherein the cell comprises a Salinispora cell. Example 87: The method of any example herein, particularly examples 83-86, wherein the cell comprises a Salinispora pacifica cell. Other advantages which are obvious and which are inherent to the invention will be evident to one skilled in the art. It will be understood that certain features and sub-combinations are of utility and may be employed without reference to other features and sub-combinations. This is contemplated by and is within the scope of the claims. Since many possible embodiments may be made of the invention without departing from the scope thereof, it is to be understood that all matter herein set forth or shown in the accompanying drawings is to be interpreted as illustrative and not in a limiting sense. The compositions and methods of the appended claims are not limited in scope by the specific compositions methods described herein, which are intended as illustrations of a few aspects of the claims and any compositions and methods that are functionally equivalent are intended to fall within the scope of the claims. Various modifications of the compositions and methods in addition to those shown and described herein are intended to fall within the scope of the appended claims. Further, while only certain representative method steps disclosed herein are specifically described, other combinations of the method steps also are intended to fall within the scope of the appended claims, even if not specifically recited. Thus, a combination of steps, elements, components, or constituents may be explicitly mentioned herein or less, however, other combinations of steps, elements, components, and constituents are included, even though not explicitly stated.

Claims

CLAIMS What is claimed:

1. A compound defined by Formula I:wherein R1is hydrogen, halide, substituted or unsubstituted C1-C20 alkyl, substituted or unsubstituted C3-C20cycloalkyl, substituted or unsubstituted C1-C20alkoxy, substituted or unsubstituted C3-C20 aryl (e.g., substituted or unsubstituted phenyl), substituted or unsubstituted C4-C21 alkylaryl, NRxRy, or ORa; R2is hydrogen, halide, substituted or unsubstituted C1-C20alkyl, substituted or unsubstituted C3-C20cycloalkyl, substituted or unsubstituted C1-C20alkoxy, substituted or unsubstituted C3-C20 aryl (e.g., substituted or unsubstituted phenyl), substituted or unsubstituted C4-C21alkylaryl, NRxRy, or ORb; R3is hydrogen, hydroxyl, halide, substituted or unsubstituted C1-C20alkyl, substituted or unsubstituted C1-C20 acyl, substituted or unsubstituted C1-C20 alkoxy, substituted or unsubstituted C1-C20 amide, NRxRy, or one or more amino acids (e.g., one or more canonical or non-canonical amino acids); Raand Rbare each independently hydrogen, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C3-C10 aryl (e.g., substituted or unsubstituted phenyl), or substituted or unsubstituted C4-C11alkylaryl; and Rxand Ryare independently selected from hydrogen, or substituted or unsubstituted C1- C5 alkyl, or substituted or unsubstituted C1-C5 acyl; or a derivative or salt thereof.

2. The compound of claim 1, wherein R1is ORaand / or R2is ORb.

3. The compound of claim 1 or claim 2, wherein the compound is defined by Formula II:wherein R3is hydrogen, hydroxyl, halide, substituted or unsubstituted C1-C20 alkyl, substituted or unsubstituted C1-C20acyl, substituted or unsubstituted C1-C20alkoxy, substituted or unsubstituted C1-C20 amide, NRxRy, or one or more amino acids (e.g., one or more canonical or non-canonical amino acids); Raand Rbare each independently hydrogen, substituted or unsubstituted C1-C10alkyl, substituted or unsubstituted C3-C10aryl (e.g., substituted or unsubstituted phenyl), or substituted or unsubstituted C4-C11 alkylaryl; and Rxand Ryare independently selected from hydrogen, or substituted or unsubstituted C1- C5alkyl, or substituted or unsubstituted C1-C5acyl; or a derivative or salt thereof.

4. The compound of any one of claims 1-3, wherein Raand / or Rbis hydrogen.

5. The compound of any one of claims 1-4, wherein the compound is defined by Formula III:wherein R3is hydrogen, hydroxyl, halide, substituted or unsubstituted C1-C20 alkyl, substituted or unsubstituted C1-C20acyl, substituted or unsubstituted C1-C20alkoxy, substituted orunsubstituted C1-C20amide, NRxRy, or one or more amino acids (e.g., one or more canonical or non-canonical amino acids); Rais hydrogen, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C3- C10aryl (e.g., substituted or unsubstituted phenyl), or substituted or unsubstituted C4-C11alkylaryl; and Rxand Ryare independently selected from hydrogen, or substituted or unsubstituted C1- C5alkyl, or substituted or unsubstituted C1-C5acyl; or a derivative or salt thereof.

6. The compound of any one of claims 1-5, wherein the compound is defined by Formula IV:wherein R3is hydrogen, hydroxyl, halide, substituted or unsubstituted C1-C20 alkyl, substituted or unsubstituted C1-C20 acyl, substituted or unsubstituted C1-C20 alkoxy, substituted or unsubstituted C1-C20amide, NRxRy, or one or more amino acids (e.g., one or more canonical or non-canonical amino acids); and Rxand Ryare independently selected from hydrogen, or substituted or unsubstituted C1- C5alkyl, or substituted or unsubstituted C1-C5acyl; or a derivative or salt thereof.

7. The compound of any one of claims 1-6, wherein R3is one or more amino acids (e.g., one or more canonical or non-canonical amino acids).

8. The compound of any one of claims 1-7, wherein R3is one or more amino acids, each amino acid independently being selected from the group consisting of Arginine (Arg), Ne- hydroxyarginine, dehydro‐3‐methylaspartate, and Valine (Val).

9. The compound of any one of claims 1-8, wherein the compound is defined by Formula V:wherein R4and R5are each independently hydrogen, hydroxyl, halide, substituted or unsubstituted C1-C20alkyl, substituted or unsubstituted C1-C20acyl, substituted or unsubstituted C1-C20alkoxy, substituted or unsubstituted C1-C20 amide, NRxRy, or one or more amino acids (e.g., one or more canonical or non-canonical amino acids); and Rxand Ryare independently selected from hydrogen, or substituted or unsubstituted C1- C5 alkyl, or substituted or unsubstituted C1-C5 acyl; or a derivative or salt thereof.

10. The compound of claim 9, wherein R4and R5are each independently one or more amino acids (e.g., one or more canonical or non-canonical amino acids), or a derivative or salt thereof.

11. The compound of claim 9 or claim 10, wherein R4and R5are each independently one or more amino acids, each amino acid independently being selected from the group consisting of Arginine (Arg), Ne-hydroxyarginine, dehydro‐3‐methylaspartate, and Valine (Val), or a derivative or salt thereof.

12. The compound of any one of claims 1-11, wherein the compound comprises AmPn-Arg- Val-DMA, AmPn-Ne-hydroxyarginine-Val-Ac, AmPn-Arg-Val-Ac, a derivative or salt thereof, or a combination thereof.

13. The compound of any one of claims 1-12, wherein the compound is selected from the group consisting of:, , or salts thereof, and combinations thereof.

14. The compound of any one of claims 1-13, wherein the compound is selected from the group consisting of:

15. The compound of any one of claims 1-14, wherein the compound is selected from the group consisting of:combinations thereof.

16. The compound of any one of claims 1-15, wherein the compound is selected from the group consisting of:,, derivatives or salts thereof, and combinations thereof.

17. The compound of any one of claims 1-16, wherein the compound is a salt.

18. The compound of any one of claims 1-17, wherein the compound is a salt form of Formula I, Formula II, Formula III, Formula IV, Formula V, or a combination thereof with a counterion.

19. The compound of any one of claims 1-18, wherein the compound is a salt form of Formula II with a counterion.

20. The compound of any one of claims 1-19, wherein the compound is a salt form of Formula II with a counterion and the salt form of the compound is selected from the group consisting of:and combinations thereof.

21. The compound of any one of claims 18-20, wherein the counterion is a monovalent or divalent counterion.

22. The compound of any one of claims 18-21, wherein the counterion is selected from the group consisting of sodium, potassium, calcium, lithium, magnesium, manganese, ammonium, iron, and combinations thereof.

23. The compound of any one of claims 1-22, wherein the compound is a potassium salt, sodium salt, calcium salt, iron salt, ammonium salt, or a combination thereof.

24. The compound of any one of claims 1-23, wherein the compound comprises an agriculturally acceptable salt thereof and / or a pharmaceutically acceptable salt thereof.

25. The compound of any one of claims 1-24, wherein the compound is a tetra-peptide.

26. The compound of any one of claims 1-25, wherein the compound is an isolate of a marine organism, or a derivative or salt thereof.

27. The compound of any one of claims 1-26, wherein the compound is a Salinispora isolate or a derivative or salt thereof.

28. The compound of any one of claims 1-27, wherein the compound is a Salinispora pacifica isolate or a derivative or salt thereof.

29. A composition comprising the compound of any one of claims 1-28.

30. The composition of claim 29, wherein the composition further comprises one or more agriculturally acceptable and / or pharmaceutically acceptable carriers.

31. The composition of claim 29 or claim 30, wherein the composition comprises a pharmaceutical composition, an agricultural composition, or a combination thereof.

32. The composition of any one of claims 29-31, wherein the composition comprises a pesticide.

33. The composition of any one of claims 29-32, wherein the composition comprises an herbicide.

34. The composition of any one of claims 29-33, wherein the composition exhibits antimicrobial activity.

35. The composition of any one of claims 29-34, wherein the composition results in at least 5 log reduction of a population of microbes.

36. The composition of claim 35, wherein the microbes are one or more microorganisms selected from the group consisting of gram negative bacteria.

37. The composition of claim 35 or claim 36, wherein the microbes are one or more microorganisms selected from the group consisting of Escherichia coli, Serratia marcescens, and Pantoea ananatis.

38. The composition of any one of claims 29-37, further comprising a solvent, a carrier, an excipient, or a combination thereof.

39. The composition of any one of claims 29-38, further comprising an agriculturally acceptable adjuvant or carrier.

40. The composition of any one of claims 29-39, wherein the composition is formulated for delivery to a plant or animal.

41. The composition of any one of claims 29-40, wherein the composition is formulated for delivery to a plant.

42. The composition of claim 41, wherein the plant comprises a crop.

43. The composition of claim 41 or claim 42, wherein the composition is formulated for delivery to onions.

44. The composition of any one of claims 29-40, wherein the composition is formulated for delivery to an animal.

45. The composition of claim 44, wherein the animal is a companion animal, livestock, research animal, insect, or human.

46. The composition of claim 44 or claim 45, wherein the animal is an insect.

47. The composition of claim 46, wherein the insect is a bee, such as a honeybee.

48. A nucleic acid encoding the compound or composition of any one of claims 1-47.

49. A vector encoding the nucleic acid of claim 48.

50. A cell comprising the vector of claim 49.

51. A cell comprising the compound or composition of any one of claims 1-47.

52. The cell of claim 50 or claim 51, wherein the cell comprises a marine organism cell.

53. The cell of any one of claims 50-52, wherein the cell comprises an actinobacterium cell.

54. The cell of any one of claims 50-53, wherein the cell comprises a Salinispora cell.

55. The cell of any one of claims 50-54, wherein the cell comprises a Salinispora pacifica cell.

56. A method of making the compound of any one of claims 1-28.

57. The method of claim 56, wherein the method is a biosynthetic method.

58. The method of claim 56 or claim 57, wherein the method uses one or more enzymes derived from Salinispora, such as Salinispora pacifica.

59. A method of use of the compound, composition, nucleic acid, vector, and / or cell of any one of claims 1-55.

60. The method of claim 59, wherein the method comprises using the compound, composition, nucleic acid, vector, and / or cell as an antimicrobial, herbicide, pesticide, or combination thereof to control an undesirable population.

61. The method of claim 60, wherein the method comprises using the compound, composition, nucleic acid, vector, and / or cell as a pesticide.

62. The method of claim 61, wherein the method comprises using the compound, composition, nucleic acid, vector, and / or cell to control an undesirable population in plants.

63. The method of claim 62, wherein the method comprises contacting the plants or the locus thereof with or applying to the soil or water the compound, composition, nucleic acid, vector, and / or cell.

64. The method of any one of claims 61-63, further comprising applying an additional pesticide.

65. The method of any one of claims 60-64, wherein the undesirable population is an herbicide resistant or tolerant population, a pesticide resistant or tolerant population, an antimicrobial resistant or tolerant population, or a combination thereof.

66. The method of any one of claims 60-65, wherein the undesirable population comprises bacteria.

67. A method of reducing the activity of bacteria, the method comprising exposing the bacteria to an effective amount of the compound, composition, nucleic acid, vector, and / or cell of any one of claims 1-55.

68. A method of reducing bacterial population, the method comprising exposing the bacteria to an effective amount of the compound, composition, nucleic acid, vector, and / or cell of any one of claims 1-55.

69. A method of killing bacteria, the method comprising exposing the bacteria to an effective amount of the compound, composition, nucleic acid, vector, and / or cell of any one of claims 1- 55.

70. A method for treating, preventing, inhibiting, and / or ameliorating a disease or disorder in a plant or a subject in need thereof, the method comprising administering to the plant or subject a therapeutically effective amount of the compound, composition, nucleic acid, vector, and / or cell of any one of claims 1-55.

71. The method of claim 70, wherein the disease or disorder comprises an infection, such as a microbial infection.

72. A method for treating, preventing, inhibiting, and / or ameliorating a microbial infection in a plant or a subject, comprising administering to the plant or subject an effective amount of the compound, composition, nucleic acid, vector, and / or cell of any one of claims 1-55.

73. The method of claim 71 or claim 72, wherein the microbial infection comprises a bacterial infection.

74. The method of any one of claims 66-73, wherein the bacteria comprise gram negative bacteria.

75. The method of any one of claims 66-74, wherein the bacteria comprise one or more bacteria selected from the group consisting of Escherichia coli, Serratia marcescens, and Pantoea ananatis.

76. The method of any one of claims 70-75, wherein the plant is a crop.

77. The method of any one of clams 70-76, wherein the plant is an onion.

78. The method of any one of claims 70-75, wherein the subject is an animal.

79. The method of claim 78, wherein the animal is a companion animal, livestock, research animal, insect, or human.

80. The method of claim 78 or claim 79, wherein the animal is an insect.

81. The method of claim 80, wherein the insect is a bee, such as a honeybee.

82. The method of any one of claims 60-81, wherein the compound, composition, nucleic acid, and / or vector is delivered via cultured Salinispora pacifica.

83. A method of isolating and / or purifying a compound produced by a cell, wherein the compound comprises the compound of any one of claims 1-28.

84. The method of claim 83, wherein the cell comprises a marine organism cell.

85. The method of any one of claims 83-84, wherein the cell comprises an actinobacterium cell.

86. The method of any one of claims 83-85, wherein the cell comprises a Salinispora cell.

87. The method of any one of claims 83-86, wherein the cell comprises a Salinispora pacifica cell.

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