Antibiotic compositions and methods of use thereof

Abstract

Provided herein are antibiotic compositions containing halogenated pyrroloketoindane compounds. Also provided herein are methods for producing the compounds and compositions described herein, and methods of using the compounds and compositions provided herein.

Description

[0001]Attorney Docket No.15670-0420WO1 ANTIBIOTIC COMPOSITIONS AND METHODS OF USE THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application Serial No. 63 / 644,590, filed on May 9, 2024. The entire contents of the foregoing are incorporated herein by reference. STATEMENT AS TO FEDERALLY SPONSORED RESEARCH This invention was made with Government support under Grant No. GM085770 awarded by the National Institutes of Health. The Government has certain rights in the invention. TECHNICAL FIELD This document relates to antibiotic compositions containing halogenated pyrroloketoindane compounds, to methods of producing the compositions provided herein, and to methods of using the compositions provided herein. For example, this document relates to di- and trichlorinated pyrroloketoindane antibiotic compounds, methods for producing the compounds, and methods for their use. BACKGROUND Twenty-eight percent of drugs approved by the FDA in 2021 contained at least one halogen atom (Benedetto Molecules 2022, 27 (5), 1643). The presence of these electronegative atoms can increase compound bioactivity, as observed for the antibiotic vancomycin (Elsocht Int J Mol Sci 2021, 22 (2), 635 and Harris J Am Chem Soc 1985, 107 (23), 6652–6658) and the anticancer drug salinosporamide A (Groll J Am Chem Soc 2006, 128 (15), 5136–5141). The biological activity of halogenated natural products makes them attractive targets for drug discovery. The abundance of halogen atoms in the marine environment provides a unique opportunity for the discovery of new halogenated metabolites. In 2015, it was estimated that more than 5,000 halogenated natural products had been discovered, with the majority produced by marine organisms including bacteria (Gribble Mar Drugs 2015, 13 (7), 4044–4136). Among marine bacteria, the MAR4 group of marine-derived Streptomyces have yielded a wide diversity of halogenated natural Attorney Docket No.15670-0420WO1 products (Sweeney J Nat Prod 2024, 87 (2), 439–452), including phenazines (Asolkar Tetrahedron 2017, 73 (16), 2234–2241), nitropyrroles (Kwon J Nat Prod 2010, 73 (12), 2047–2052 and Raju Sp. Org Lett 2010, 12 (22), 5158–5161), and tetrahydroxynaphthalene (THN) derived molecules (Carretero-Molina Mar Drugs 2019, 18 (1), 22; Pereira Mar Drugs 2020, 18 (1), 63; Cheng European J Org Chem 2013, 2013 (18), 3751–3757; and Pathirana Tetrahedron Lett 1992, 33 (50), 7663– 7666; Hardt Tetrahedron Lett 2000, 41 (13), 2073–2076). In addition to the compounds already discovered from this group, genome mining has revealed halogenases in orphan biosynthetic gene clusters (BGCs), suggesting that additional halogenated metabolites await discovery (Bauermeister Environ Microbiol 2019, 21 (3), 1099–1112 and Gallagher BMC Genomics 2015, 16 (1), 960). One approach to facilitate natural product discovery involves pairing genomic and metabolomic data through a process known as pattern-based genome mining or metabologenomics (Duncan Chem Biol 2015, 22 (4), 460–471 and Goering ACS Cent Sci 2016, 2 (2), 99–108). This method correlates gene cluster families with ions detected by mass spectrometry (MS), enabling the connection of both known and novel metabolites to orphan BGCs as has been shown in the marine actinomycete Salinispora (Duncan Chem Biol 2015, 22 (4), 460–471) and other bacteria (Goering ACS Cent Sci 2016, 2 (2), 99–108). Recent advances in this process include tools such as NPLinker (Hjörleifsson PLoS Comput Biol 2021, 17 (5), e1008920) and NPOmix (Leão PNAS Nexus 2022, 1 (5), 1–15), which use correlation-based statistics and machine learning to link metabolites to their cognate BGCs. Halogenated natural products are suited for pattern-based genome mining due to their distinctive MS isotopic signatures. The incorporation of moieties derived from amino acids can be predicted based on adenylation domain specificity. Linking structural and biosynthetic hooks can facilitate the discovery of novel halogenated metabolites, with BGCs providing added insights into structure assignments. These techniques are also applicable to BGC subclusters as shown in the biosynthesis of pyrrole and chloropyrrole starter units in chlorizidine (Mantovani J Am Chem Soc 2013, 135 (48), 18032–18035), armeniaspirol (Fu ChemBioChem 2019, 20 (6), 764–769), and marinopyrrole (Yamanaka J Am Chem Soc 2012, 134 (30), 12434–12437), among others. Attorney Docket No.15670-0420WO1 SUMMARY This document is based, at least in part, on the discovery of novel di- and trichlorinated pyrroloketoindane compounds that can have, for example, antibiotic and / or insecticide activity. This document also is based, at least in part, on the identification of the distribution of the candidate BGCs among MAR4 strains and global sequence databases. In a first aspect, this document features a composition containing, consisting essentially of, or consisting of a carrier (e.g., a pharmaceutically acceptable carrier) and an isolated and / or purified compound of Formula (I): wherein R1, R2, and R3are each independently H or halogen; and R4, R5, R6, and R7are each independently H, -CH3, and -CH2CH3; and wherein the carrier is not water. The compound of Formula (I) can be a compound of Formula (Ia): Formula (Ia) or a R1can be H. R1ca be -Cl. R3can be H. R3can be -Cl. R1can be -Cl, R2can be -Cl, and R3can be -Cl. R1can be H, R2can be -Cl, and R3can be -Cl. R4can be -CH3. R5can be -CH3. R6can be-CH3. R7can be H. In some cases, the compound of Formula (I) can be Compound 1 or Compound 2: Attorney Docket No.15670-0420WO1 or or a 1a or Compound 2a: or or a For example, the compound of Formula (I) can be Compound 1a Attorney Docket No.15670-0420WO1 (Compound 1a) or a (I) can be Compound 2a (Compound 2a) or a The carrier can be selected from the group consisting of saline solution, binding agents, fillers, lubricants, disintegrants, and wetting agents. In another aspect, this document features an article of manufacture containing a composition as described herein, where the article of manufacture optionally includes instructions for use of the composition as an antibiotic and / or an insecticide. In another aspect, this document features a method for producing an isolated and purified Compound 1, Compound 1a, Compound 2, or Compound 2a: , , Attorney Docket No.15670-0420WO1 or of: culturing a bacteria in media containing starch, yeast extract, peptone, instant ocean, and KBr; incubating the cultured bacteria with XAD-7 resin; filtering the resin-treated bacteria, washing the filtered bacteria with water, eluting the washed bacteria with methanol, and evaporating the methanol to generate a crude extract; and purifying Compound 1, Compound 1a, Compound 2, or Compound 2a using vacuum liquid chromatography and / or high-performance liquid chromatography (HPLC). The bacteria can be strain CNY-716 of MAR4 Streptomyces. The method can include culturing the population of bacteria for 10 days. The purifying can include fractionating crude extract using vacuum liquid chromatography and a step wise methanol:water (MeOH:H2O) gradient. The step wise MeOH:H2O gradient can include eight fractions having ratios of: (1) 25:75 MeOH:H2O, (2) 50:50 MeOH:H2O, (3) 60:40 MeOH:H2O, (4) 70:30 MeOH:H2O, (5) 80:20 MeOH:H2O, (6) 90:10 MeOH:H2O, and (7 and 8) 100% MeOH. Fractions (6) and (7) can include indanopyrroles. The method can include using HPLC to purify Compound 1, Compound 1a, Compound 2, or Compound 2a from fractions (6) and (7). In still another aspect, this document features a method for producing an isolated Compound 1, Compound 1a, Compound 2, or Compound 2a: Attorney Docket No.15670-0420WO1 or where of: expressing, in a host cell cultured in a culture medium: a first recombinant nucleic acid encoding a first polypeptide having metalloregulator ArsR / SmtB activity, a second recombinant nucleic acid encoding a polypeptide having phosphopentetheinyl transferase activity, a third recombinant nucleic acid encoding a second polypeptide having metalloregulator ArsR / SmtB activity, a fourth recombinant nucleic acid encoding a polypeptide having acyl-CoA dehydrogenase activity, a fifth recombinant nucleic acid encoding a polypeptide having amino acid adenylation activity, a sixth recombinant nucleic acid encoding a polypeptide having acyl carrier activity, a seventh recombinant nucleic acid encoding a polypeptide having tryptophan halogenase Attorney Docket No.15670-0420WO1 activity, an eighth recombinant nucleic acid encoding a first polypeptide having T1 polyketide synthase (PKS) activity, a ninth recombinant nucleic acid encoding a second polypeptide having T1PKS activity, a tenth recombinant nucleic acid encoding a third polypeptide having T1PKS activity, an eleventh recombinant nucleic acid encoding a fourth polypeptide having T1PKS activity, and a twelfth recombinant nucleic acid encoding a polypeptide having thioesterase / hydrolase activity, to produce Compound 1, Compound 1a, Compound 2, or Compound 2a; and isolating Compound 1, Compound 1a, Compound 2, or Compound 2a from the culture medium. In another aspect, this document features a method for preparing a composition containing Compound 1, Compound 1a, Compound 2, or Compound 2a: or Attorney Docket No.15670-0420WO1 (Compound 2a) where essentially of: culturing a in media containing starch, yeast extract, peptone, instant ocean, and KBr; incubating the cultured bacteria with XAD-7 resin; filtering the resin-treated bacteria, washing the filtered bacteria with water, eluting the washed bacteria with methanol, and evaporating the methanol to generate a crude extract; purifying the Compound 1, Compound 1a, Compound 2, or Compound 2a using vacuum liquid chromatography and / or high-performance liquid chromatography (HPLC); and combining the compound with a carrier (e.g., a pharmaceutically acceptable carrier). The MAR4 Streptomyces can be strain CNY-716. The method can include culturing the population of bacteria for 10 days. The purifying can include fractionating a crude extract using vacuum liquid chromatography and a step wise methanol:water (MeOH:H2O) gradient. The step wise MeOH:H2O gradient can include eight fractions having ratios of: (1) 25:75 MeOH:H2O, (2) 50:50 MeOH:H2O, (3) 60:40 MeOH:H2O, (4) 70:30 MeOH:H2O, (5) 80:20 MeOH:H2O, (6) 90:10 MeOH:H2O, and (7 and 8) 100% MeOH. Fractions (6) and (7) can include indanopyrroles. The method can include using HPLC to purify Compound 1, Compound 1a, Compound 2, or Compound 2a from fractions (6) and (7). The carrier can be selected from the group consisting of saline solution, binding agents, fillers, lubricants, disintegrants, and wetting agents. In yet another aspect, this document features a method for preparing a composition containing Compound 1, Compound 1a, Compound 2, or Compound 2a: , Attorney Docket No.15670-0420WO1 or where of: expressing, in a host cell cultured in a culture medium: a first recombinant nucleic acid encoding a first polypeptide having metalloregulator ArsR / SmtB activity, a second recombinant nucleic acid encoding a polypeptide having phosphopentetheinyl transferase activity, a third recombinant nucleic acid encoding a second polypeptide having metalloregulator ArsR / SmtB activity, a fourth recombinant nucleic acid encoding a polypeptide having acyl-CoA dehydrogenase activity, a fifth recombinant nucleic acid encoding a polypeptide having amino acid adenylation activity, a sixth recombinant nucleic acid encoding a polypeptide having acyl carrier activity, a seventh recombinant nucleic acid encoding a polypeptide having tryptophan halogenase activity, an eighth recombinant nucleic acid encoding a first polypeptide having T1 polyketide synthase (PKS) activity, a ninth recombinant nucleic acid encoding a second polypeptide having T1PKS activity, a tenth recombinant nucleic acid encoding a third polypeptide having T1PKS activity, an eleventh recombinant nucleic acid encoding a fourth polypeptide having T1PKS activity, and a twelfth recombinant nucleic acid encoding a polypeptide having thioesterase / hydrolase activity, to produce Attorney Docket No.15670-0420WO1 Compound 1, Compound 1a, Compound 2, or Compound 2a; isolating Compound 1, Compound 1a, Compound 2, or Compound 2a from the culture medium; and combining the compound with a carrier (e.g., a pharmaceutically acceptable carrier). The carrier can be selected from the group consisting of saline solution, binding agents, fillers, lubricants, disintegrants , and wetting agents. In another aspect, this document features a method for killing bacteria, where the method includes, consists of, or consists essentially of contacting the bacteria with a composition provided herein, where the composition contains an effective concentration of the compound of Formula (I). The bacteria can include Gram negative bacteria. The bacteria can include Gram positive bacteria. The bacteria can include one or more of Staphylococcus, Streptococcus, Enterococcus, Haemophilus, Escherichia, and Acinetobacter (e.g., one or more of Staphylococcus aureus, Enterococcus faecium, Staphylococcus epidermidis, Haemophilus influenzae, Escherichia coli, and Acinetobacter baumannii). The effective concentration can be about 0.5 µg / mL to about 5 µg / mL. The effective concentration can be greater than about 15 µg / mL. The method can be carried out in vitro or in vivo. In another aspect, this document features a method for killing an insect, where the method includes, consists of, or consists essentially of contacting the insect with a composition provided herein, where the composition contains an effective concentration of the compound of Formula (I). The insect can be a fly, a gnat, a cabbage worm, a potato beetle, or a cotton aphid). The effective concentration can be about 0.5 µg / mL to about 5 µg / mL. The effective concentration can be greater than about 15 µg / mL. 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. Methods and materials are described herein for use in the present invention; other, suitable methods and materials known in the art can also be used. The materials, methods, and examples are illustrative only and not intended to be limiting. All publications, patent applications, patents, sequences, database entries, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. Attorney Docket No.15670-0420WO1 Other features and advantages of the invention will be apparent from the following detailed description and figures, and from the claims. DESCRIPTION OF THE DRAWINGS FIGS.1A-1C illustrate a proposed indanopyrrole BGC and biosynthetic scheme. FIG.1A. Proposed indanopyrrole (Idp) BGC from CNX-425 compared to the indanomycin BGC (Idm, MIBiG #: BGC0000079). FIG.1B. Idp gene annotations based on top BLAST matches to the NCBI NR / NT database. FIG.1C. Representative biosynthesis method for compound 1a in concordance with the Idp BGC. Cryptic dehydration of the hydroxy moiety (circled) is proposed to afford an alkene that undergoes a Diels-Alder ([4+2] cycloaddition) reaction to form the indane ring in the final indanopyrrole molecule. IdpD, idp dehydrogenase module; IdpE, idp proline adenyltransferase module; IdpF, idp proline carrier protein module; IdpG, idp tryptophan halogenase module; KS, ketosynthase; AT, acyltransferase; ACP, acyl carrier protein; mAT, malonyl acetyltransferase; KR, ketoreductase; ER, enoylreductase; DH, dehydratase; TE, thioesterase. FIG.2 illustrates the results of a database search for idp and idm BGCs. Seven idp and idm homologs were identified from a GenBank search, highlighting the rarity of these BGCs. The matches presented represent those BGCs with strong gene synteny to the queries. FIG.3 is an MS spectrum of compound 1a. FIG.4 is an annotated MS / MS spectrum of compound 1a. FIG.5 includes a series of LCMS spectra showing production of compound 1a in Streptomyces sp. strain CNY-716, with LCMS analysis of the same 1 L culture over time. Extracted ion chromatograms (m / z 458.10-458.11) Upper: EtOAc extract of a 20 mL aliquot on day 7. Middle: EtOAc extract of a 20 mL aliquot on day 10. Lower: XAD-7 resin extraction on day 14 (resin added on day 10). FIGS.6A-6C show structure elucidation of compound 1a. FIG.6A. COSY (bold bonds) and key HMBC (arrows) correlations. FIG.6B and FIG.6C.3D model of minimal energy optimized conformer (Est. Density Functional ωB97X-D / 6-31G*, 200.51 kJ / mol, 96.6% Boltzmann distribution). FIG.7 is an MS spectrum of compound 2a. FIG.8 is an annotated MS / MS spectrum of compound 2a. Attorney Docket No.15670-0420WO1 FIG.9 shows synteny plots of all Indanopyrrole BGCs found within the MAR4 genome. Bars in the MS1 column indicate positive hits for the indanopyrrole m / z for this strain in this small-scale survey. The first four strain ID backgrounds share >95% ANI, and the other 16 strain ID backgrounds share <95% ANI. FIG.10A shows an idp and idm terminal KS phylogeny. The phylogeny includes KS sequences from the NaPDoS2 database plus the KS domains from the starting (upper branches) and last (lower left and center branches) PKS modules in all MAR4 idp gene clusters. The starting KS domains (upper branches) clade with those from other BGCs incorporate pyrrole starter units. The pyrrole starter unit in pyralomycin undergoes an uncharacterized rearrangement in the late-stage biosynthesis. The terminal KS domains are most similar to another “inactive” KS domain from salinomycin. Other non-elongating KS domains from trans-AT BGCs, including the ring forming salinosporamide and cinnabaramide KS domains, are shown (lower and middle right). FIG.10B shows pyrroloindane containing natural products with pyrrole and indane rings circled. FIG.11 is an alignment of module 2 ketoreductase (KR) domain sequences from idpH and other A2-type KR domains, showing the absence of the LDD motif (box 1) associated with B-type domains and containing the active site tryptophan (box 2) and histidine (box 3) associated with A2-type domains, which are known to generate SS chemistry at the newly created stereocenter. FIG.12 is an alignment of enoylreductase (ER) domain sequences from idpJ and other ER domains, showing that idpJ is missing the active site tyrosine (box) observed in ER domains that generate S stereochemistry. FIG.13 is an alignment of ketosynthase (KS) domain sequences from idpK, which is missing the active site histidine required for decarboxylation activity (box 3). This residue is not mutated in the SalC_KS and RhiF_KS2) ‘KS0’ domains (box 2). FIG.14 shows a whole module alignment of selected Indanopyrrole and Indanomycin terminal KS modules. Individual domains were indicated by boxes above the amino acid alignment, to show the location of KS, AT, and Cyclase. Boxes indicate known active site residues of the KS and AT domains. Only indanopyrrole terminal KS modules were lacking a part of the active site catalytic triad. All terminal module AT domains were lacking all known active site residues (expanded residues, boxes). Only the indanomycin BGC from MIBiG contained the cyclase domain found Attorney Docket No.15670-0420WO1 in indanomycin. Domain boundaries based on the indanomycin BGC on the DoBISCUIT database (Ichikawa Nucleic Acids Res 2012, 41 (D1), D408–D414). FIG.15 is an alignment of the amino acid sequences of the terminal KS domains for all indanopyrrole BGCs, or fragments that contained the terminal KS module. Indanomycin is included for reference. All indanopyrrole (Ind) BGCs including that identified from the cblaster searches have a conserved tyrosine residue in the last box that is a histidine in the indanomycin producers. FIGS.16A-16B show modeling of IdpK against 6-deoxyerythronolide B synthase (DEBS) KS1. FIG.16A shows a Colabfold model of IdpK KS overlaid with DEBS KS1. The colabfold model matches well with the known 3D structure of DEBs. The inset shows the final indanopyrrole A structure in the active site and the alignment of cysteine-167 with the carboxylic acid moiety as expected in PKS biosynthesis. Histidine-302 is positioned above carbon-14 in the indanopyrrole structure possibly allowing for hydrogen abstraction and a subsequent Diels-Alder cyclization reaction to form the final product. The mesh surface indicates that the substrate binding pocket of IdpK is shaped in a way that could allow for a Diels-Alder reaction. FIG.16B shows a biosynthetic mechanism for IdpK KS to complete dehydratase activity and subsequent Diels-Alderase activity. FIG.17 shows cblaster results filtered for the presence of at least one gene with >70% similarity to any one of the query PKS genes.40 BGCs were found on the NCBI nr database webserver and could be classified into 7 BGC groups with another 9 singleton BGCs. Idp and Idm are shown at the top. FIGS.18A-18C show results from an A549 cell line LDH viability assay using compound 1a at 16, 32, and 128 µg / mL (FIG.18A, FIG.18B, and FIG.18C, respectively). Solvent vehicle (H2O:DMSO in 1:2 ratio) and untreated cells were used as negative controls. Cell lysis with Triton X-100 was used as positive control. Cell toxicity was observed at 16 µg / mL after 24 hours. FIG.19 is an1H NMR spectrum of compound 1a in MeOH-d4. FIG.20 is a13C NMR spectrum of compound 1a in MeOH-d4 (Varian, 125 MHz). FIG.21 is an1H-1H COSY spectrum of compound 1a in MeOH-d4. of compound 1a in MeOH-d4. FIG.23 is an HMBC spectrum of compound 1a in MeOH-d4. Attorney Docket No.15670-0420WO1 FIG.24 is a NOESY spectrum of compound 1a in MeOH-d4. FIG.25 is an1H NMR spectrum of compound 2a in MeOH-d4. FIG.26 is an1H-1H COSY spectrum of compound 2a in MeOH-d4. FIG.27 is an HSQC spectrum of compound 2a in MeOH-d4. FIG.28 is an HMBC spectrum of compound 2a in MeOH-d4. DETAILED DESCRIPTION Pyrroloketoindanes, characterized by indane and pyrrole ring systems bridged via a ketone, are rare natural products that represent targets for genome mining. Prior to the studies described herein, only six such compounds had been reported, with none being halogenated (structures shown Table 1 below). These molecules, all of bacterial origin, appear to be the products of polyketide synthase (PKS) BGCs. The first pyrroloketoindane described was indanomycin (3), which was identified from Streptomyces antibioticus NRRL 8167 (Westley J Antibiot (Tokyo) 1979, 32 (2), 100– 107) and demonstrated activity against Gram-positive bacteria (Liu J Antibiot (Tokyo) 1979, 32 (2), 95–99). The indanomycin analog cafamycin (4) was subsequently identified from a Streptomyces species (Murenets Antibiot Med Biotekhnol 1987, 32 (11), 811–814). Shortly thereafter, 16-deethylindanomycin (5) was isolated from Streptomyces setonii A80394A and reported to be active against Gram-positive bacteria and protist parasites (Larsen J Antibiot (Tokyo) 1988, 41 (9), 1170–1177). A compound with the same structure as 16-deethylindanomycin was published as omomycin and reported to elevate cyclic guanosine monophosphate levels in rat heart cells (Gerasimova Vopr Med Khim 1990, 36 (5), 39–41). Homoindanomycin (6) was described without any information about activity (Toth HU49909 A2, 1989), and the first indanomycin analog to lack a tetrahydropyran ring, stawamycin (7), was shown to inhibit Epstein-Barr viral transcription factor BZLF1 binding to DNA (Miao Tetrahedron Lett 1995, 36 (32), 5699–5702). Finally, JBIR-11 (8) was identified from Streptomyces viridochromogenes, subsp. sulfomycini NBRC 13830, representing an unusual analog of stawamycin that contains a tryptophan moiety. It was shown to be cytotoxic to HT1080 fibrosarcoma cells (Izumikawa J Antibiot (Tokyo) 2008, 61 (5), 326–329). Subsequent work demonstrated that indanomycin is a potent insecticide (Zhang J Antibiot (Tokyo) 1997, 50 (7), 617–620) and also possesses antiviral activity against SARS-CoV-2 (Aherfi Future Microbiol 2021, 16 (17), 1341–1370). Attorney Docket No.15670-0420WO1 Indanomycin analogs containing a tetrahydropyran ring can act as ionophores, thus providing a mechanism for their antibiotic and possibly other activities. Table 1 Name Structure Indanomycin (3) This document provides novel di- and trichlorinated pyrroloketoindane ionophore compounds, and describes the distribution of the candidate BGC among Attorney Docket No.15670-0420WO1 MAR4 strains and global sequence databases. Compositions containing the novel compounds also are provided herein, as are methods for their use (e.g., as antibiotics and / or insecticides). Compositions Provided herein are compositions that include a carrier (e.g., a pharmaceutically acceptable carrier) and an isolated and / or purified compound of Formula (I): or a pharmaceutically wherein R1, R2, and R3are each independently H or halogen; and R4, R5, R6, and R7are each independently H, -CH3, and -CH2CH3; wherein the pharmaceutically acceptable carrier is not water. In some embodiments, the compound of Formula (I) is a compound of Formula (Ia): or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is a compound of Formula (Ib): Attorney Docket No.15670-0420WO1 or a pharmaceutically In some embodiments, the compound of Formula (I) is a compound of Formula (Ic): or a In some embodiments, the compound of Formula (I) is a compound of Formula (Id): or a pharmaceutically In some embodiments, the compound of Formula (I) is a compound of Formula (Ie): Attorney Docket No.15670-0420WO1 or a pharmaceutically In some embodiments of formulas Ia-Ie, R1is H or halogen; R2is halogen; and R3is halogen. In some embodiments of formulas Ia-Ie, R1is H. In some embodiments, R1is - Cl, -Br, or -I. In some embodiments, R1is -Cl. In some embodiments, R2is -Cl, -Br, or -I. In some embodiments, R2is -Cl. In some embodiments, R3is -Cl, -Br, or -I. In some embodiments, R3is -Cl. In some embodiments of formulas Ia-Ie, R1is -Cl, R2is -Cl, and R3is -Cl. In some embodiments, R1is H, R2is -Cl, and R3is -Cl. In some embodiments, R1is -Cl, R2is H, and R3is -Cl. In some embodiments, R1is -Cl, R2is -Cl, and R3is H. In some embodiments, R1is -Cl, R2is H, and R3is H. In some embodiments, R1is H, R2is - Cl, and R3is H. In some embodiments, R1is H, R2is H, and R3is -Cl. In some embodiments of formulas Ia-Ie, R4is -CH3. In some embodiments, R4is H. In some embodiments, R4is -CH2CH3. In some embodiments of formulas Ia-Ie, R5is -CH3. In some embodiments, R5is H. In some embodiments, R5is -CH2CH3. In some embodiments of formulas Ia-Ie, R6is -CH3. In some embodiments, R6is H. In some embodiments, R6is -CH2CH3. In some embodiments of formulas Ia-Ie, R7is H. In some embodiments, R7is H. In some embodiments, R7is -CH2CH3. In some embodiments of formulas Ia-Ie, R4is -CH3and R5is -CH3. In some embodiments of formulas Ia-Ie, R4is -CH3, R5is -CH3, R6is -CH3, and R7is H. In some embodiments, the compound of Formula (I) is Compound 1 or Compound 2: Attorney Docket No.15670-0420WO1 or (I) is Compound 1a or or In some embodiments, the compound of Formula (I) is Compound 1a Attorney Docket No.15670-0420WO1 (Compound 1a) of thereof. some of Formula (I) is Compound 2a (Compound 2a) of thereof. The compositions provided herein can include one or more carriers. For example, any appropriate pharmaceutically acceptable carrier can be included. Non- limiting examples of suitable pharmaceutically acceptable carriers include saline, solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, sterile aqueous or non-aqueous solutions, suspensions, emulsions, and the like, that are compatible with pharmaceutical administration. Examples of non-aqueous solvents include, without limitation, propylene glycol, polyethylene glycol, vegetable oils, and organic esters. Aqueous carriers include, without limitation, water, alcohol, saline, and buffered solutions. Acceptable carriers also can include physiologically acceptable aqueous vehicles (e.g., physiological saline) or other known carriers for oral administration. In some embodiments, the one or more carriers in a composition provided herein can be selected from the group consisting of saline solution, binding agents (e.g., polyvinylpyrrolidone and / or hydroxypropyl methylcellulose); fillers (e.g., lactose or dextrose and other sugars, gelatin, and / or calcium sulfate); lubricants (e.g., starch, polyethylene glycol, and / or sodium acetate); disintegrants (e.g., starch and / or sodium starch glycolate); and wetting agents (e.g., sodium lauryl sulfate). Attorney Docket No.15670-0420WO1 Pharmaceutical compositions typically are formulated to be compatible with their intended route of administration or use. For example, the compositions provided herein can be formulated for oral administration, topical administration, or parenteral (e.g., intravenous, intradermal, subcutaneous, intramuscular, airway (aerosol), and subcutaneous) administration to a vertebrate (e.g., a human, a non-human primate, a cow, a horse, a sheep, a goat, a pig, a fish, a dog, a cat, a rabbit, a rat, or a mouse). In some embodiments, the compositions provided herein can be formulated for application to a surface (e.g., in an aerosol or liquid spray). In some embodiments, the surface can be a plant or a plant part. In some embodiments, the composition includes culture medium containing a compound described herein (e.g., in the presence of host cells). In some embodiments, the compositions provided herein can be formulated for application to crops. The compositions provided herein can have any appropriate form. For example, a composition provided herein can be in the form of a liquid, solution, suspension, tablet, powder, granule, pill, capsule, gel, cream, mist, atomized vapor, aerosol, soft gelatin capsule, or hard gelatin capsule. For oral administration, tablets or capsules can be prepared with one or more excipients (e.g., one or more pharmaceutically acceptable excipients) such as binding agents, fillers, lubricants, disintegrants, or wetting agents. In some cases, the tablets can be coated . Liquid preparations for oral administration can take the form of, for example, solutions, syrups, or suspension, or they can be presented as a dry product for constitution with saline or other suitable liquid vehicle before use. Liquid preparations also can contain one or more additives (e.g., one or more pharmaceutically acceptable additives) such as suspending agents, emulsifying agents, non-aqueous vehicles, preservatives, buffer salts, flavoring agents, coloring agents, and sweetening agents as appropriate. Preparations for oral administration can be suitably formulated to give controlled release of a compound provided herein. In some embodiments, a pharmaceutical composition provided herein can be formulated for oral ingestion, injection (e.g., subcutaneous injection), or tissue-specific targeting. In some cases, a composition provided herein can be in a form suitable for application to an inanimate object (e.g., a marine surface or a farming implement,). This document also provides articles of manufacture containing one or more compositions described herein. The articles of manufacture optionally can include Attorney Docket No.15670-0420WO1 instructions for use of a composition provided herein as an antibiotic and / or an insecticide. Methods of Producing Also provided herein are methods for producing isolated and purified compounds of Formula (I). In some embodiments, the compounds provided herein can be produced in host cells or in vitro using nucleic acids as described herein. Suitable host cells include any microorganism, eukaryotic or prokaryotic, such as bacteria (e.g., Streptomyces, Escherichia coli, Staphylococcus aureus, Streptococcus, Enterococcus faecium, Staphylococcus epidermidis, Haemophilus influenzae, Acinetobacter baumannii, Bacillus, Brevibacterium, Pseudomonas), yeast (e.g., Pichia pastoris, Saccharomyces cerevisiae, Yarrowia lipolytica, Kluyveromyces marxianus, or Komagataella phaffii) and other fungi (e.g., Neurospora crassa), and green algae (e.g., Dunaliella sp., Chlorella variabilis, Euglena mutabilis, or Chlamydomonas reinhardtii). Such host cells may or may not naturally produce the compounds described herein. In some embodiments, a method provided herein can include: culturing a population of bacteria (e.g., Streptomyces such as MAR4 Streptomyces or other bacteria that contain the idp-like BGC) in media containing, for example, 10 g / L starch, 4 g / L yeast extract, 2 g / L peptone, 22 g / L instant ocean, and 0.1 g / L KBr for an appropriate length of time (e.g., seven to ten days); incubating the cultured bacteria with XAD-7 resin for an appropriate length of time (e.g., three to seven days); filtering the resin-treated bacteria, washing the filtered bacteria with water, eluting the washed bacteria with methanol, and evaporating the methanol to generate a crude extract; and purifying a compound of Formula (I) using vacuum liquid chromatography and / or high-performance liquid chromatography (HPLC), or another suitable separation technique. Attorney Docket No.15670-0420WO1 Also provided herein are methods for producing an isolated and purified Compound 1, Compound 1a, Compound 2, and / or Compound 2a. The methods can include: culturing a population of bacteria (e.g., Streptomyces such as MAR4 Streptomyces or other bacteria that contain the idp-like BGC) in media containing, for example,10 g / L starch, 4 g / L yeast extract, 2 g / L peptone, 22 g / L instant ocean, and 0.1 g / L KBr for an appropriate length of time (e.g., seven to ten days); incubating the cultured bacteria with XAD-7 resin for an appropriate length of time (e.g., three to seven days); filtering the resin-treated bacteria, washing the filtered bacteria with water, eluting the washed bacteria with methanol, and evaporating the methanol to generate a crude extract; and purifying Compound 1, Compound 1a, Compound 2, or Compound 2a using vacuum liquid chromatography and / or HPLC or other suitable chromatography methods. In some embodiments, the MAR4 Streptomyces is strain CNY-716. In some embodiments, the methods can include culturing the population of bacteria for 10 days. In some embodiments, the purification can include fractionating the crude extract using vacuum liquid chromatography and a step wise methanol:water (MeOH:H2O) gradient. In some embodiments, the step wise MeOH:H2O gradient can include fractions having ratios of: (1) 25:75 MeOH:H2O, (2) 50:50 MeOH:H2O, (3) 60:40 MeOH:H2O, (4) 70:30 MeOH:H2O, (5) 80:20 MeOH:H2O, (6) 90:10 MeOH:H2O, and (7 and 8) 100% MeOH. In some embodiments, fractions (6) and (7) can include indanopyrroles. In some embodiments, the methods can include using HPLC to purify Compound 1, Compound 1a, Compound 2, or Compound 2a from fractions (6) and (7). In some embodiments, the methods can include using HPLC to purify the compound of Formula (I) from fractions (6) and (7). In some cases, a host cell can be modified to contain one or more exogenous nucleic acids that encode polypeptides having activities for synthesis of compounds provided herein. The term “nucleic acid” as used herein encompasses both RNA and DNA, including cDNA, genomic DNA, and synthetic (e.g., chemically synthesized) Attorney Docket No.15670-0420WO1 DNA. The nucleic acid can be double-stranded or single-stranded. Where single- stranded, the nucleic acid can be the sense strand or the antisense strand. In addition, nucleic acid can be circular or linear. The term “exogenous” as used herein with reference to nucleic acid and a particular host cell refers to any nucleic acid that does not originate from that particular host cell as found in nature. Thus, non-naturally-occurring nucleic acid is considered to be exogenous to a host cell once introduced into the host cell. It is important to note that non-naturally-occurring nucleic acid can contain nucleic acid sequences or fragments of nucleic acid sequences that are found in nature provided the nucleic acid as a whole does not exist in nature. For example, a nucleic acid molecule containing a genomic DNA sequence within an expression vector is non- naturally-occurring nucleic acid, and thus is exogenous to a host cell once introduced into the host cell, since that nucleic acid molecule as a whole (genomic DNA plus vector DNA) does not exist in nature. Thus, any vector, autonomously replicating plasmid, or virus (e.g., retrovirus, adenovirus, or herpes virus) that as a whole does not exist in nature is considered to be non-naturally-occurring nucleic acid. It follows that genomic DNA fragments produced by PCR or restriction endonuclease treatment as well as cDNAs are considered to be non-naturally-occurring nucleic acid since they exist as separate molecules not found in nature. It also follows that any nucleic acid containing a promoter sequence and polypeptide-encoding sequence (e.g., cDNA or genomic DNA) in an arrangement not found in nature is non-naturally-occurring nucleic acid. A nucleic acid that is naturally-occurring can be exogenous to a particular cell. For example, an entire chromosome isolated from a cell of organism X is an exogenous nucleic acid with respect to a cell of organism Y once that chromosome is introduced into Y’s cell. It is noted that a host cell can be given an exogenous nucleic acid molecule that encodes a polypeptide having an enzymatic activity that catalyzes the production of a compound not normally produced by that host cell. Alternatively, or additionally, a host cell can be given an exogenous nucleic acid molecule that encodes a polypeptide having an enzymatic activity that catalyzes the production of a compound that is normally produced by that host cell. In this case, the recombinant host cell can Attorney Docket No.15670-0420WO1 produce more of the compound, or can produce the compound more efficiently, than a similar host cell not having the genetic modification. An polypeptide having a particular activity (e.g., a particular enzymatic activity) can be a polypeptide that is either naturally-occurring or non-naturally- occurring. A naturally-occurring polypeptide is any polypeptide having an amino acid sequence as found in nature, including wild-type and polymorphic polypeptides. Such naturally-occurring polypeptides can be obtained from any species including, without limitation, animal (e.g., mammalian), plant, fungal, and bacterial species. A non- naturally-occurring polypeptide is any polypeptide having an amino acid sequence that is not found in nature. Thus, a non-naturally-occurring polypeptide can be a mutated version of a naturally-occurring polypeptide. For example, a non-naturally- occurring polypeptide having metalloregulator ArsR / SmtB activity can be a mutated version of a naturally-occurring polypeptide having metalloregulator ArsR / SmtB activity. A polypeptide can be mutated by, for example, sequence additions, deletions, substitutions, or combinations thereof. Sequences for polypeptides having a particular activity or function (e.g., a metalloregulator ArsR / SmtB polypeptide, a phosphopentetheinyl transferase polypeptide, an acyl-CoA dehydrogenase polypeptide, an amino acid adenylase polypeptide, an acyl carrier polypeptide, a tryptophan halogenase polypeptide, a T1 polyketide synthase polypeptide, and a thioesterase / hydrolase polypeptide that can be used to synthesize a compound provided herein (e.g., as illustrated in FIG.1C) can be found elsewhere. For example, the whole genomes for two strains containing an idp- like BGC are available on GenBank (strain CNY-716 at Accession No. JBMDLE000000000, and strain CNX-425 at accession no. NZ_JBMDLF000000000. It will be appreciated that a number of nucleic acids can encode a polypeptide having a particular amino acid sequence. The degeneracy of the genetic code is well known to the art; i.e., for many amino acids, there is more than one nucleotide triplet that serves as the codon for the amino acid. For example, codons in the coding sequence for a given polypeptide can be modified such that optimal expression in a particular species (e.g., bacteria or fungus) can be attained, using appropriate codon bias tables for that species. In addition, it will be appreciated that polypeptides with structural and / or functional similarity to the polypeptides described herein are also encompassed within the scope of the document. Attorney Docket No.15670-0420WO1 This document provides recombinant host cells that can be used to produce one or more compounds as described herein. For example, an individual host cell can contain exogenous nucleic acid such that each of the encoded polypeptides are expressed. It is important to note that such host cells can contain any number and / or combination of exogenous nucleic acid molecules. For example, a particular host cell can contain any appropriate number of exogenous nucleic acids encoding the polypeptides listed herein (e.g., one or more polypeptides having metalloregulator ArsR / SmtB activity, one or more polypeptides having phosphopentetheinyl transferase activity, one or more polypeptides having metalloregulator ArsR / SmtB activity, one or more polypeptides having acyl-CoA dehydrogenase activity, one or more polypeptides having amino acid adenylation activity, one or more polypeptides having acyl carrier activity, one or more polypeptides having tryptophan halogenase activity, one or more polypeptides having PKS activity, and one or more polypeptides having thioesterase / hydrolase activity). A single exogenous nucleic acid can encode one polypeptide or more than one polypeptide (e.g., one or more copies of from one to ten (or more) polypeptides, from one to eight, from one to seven, from one to six, from one to five, from one to four, or from two to three polypeptides). Thus, the number of different exogenous nucleic acids needed to produce the polypeptides for synthesis of compounds provided herein will depend on the particular embodiment. FIG.1C provides a non-limiting schematic of suitable gene cassettes for expressing the polypeptides for synthesis of compounds provided herein. Also provided herein are methods for producing an isolated compound of Formula (I). The methods can include expressing, in a host cell cultured in a culture medium: a first recombinant nucleic acid encoding a first polypeptide having metalloregulator ArsR / SmtB activity, a second recombinant nucleic acid encoding a polypeptide having phosphopentetheinyl transferase activity, a third recombinant nucleic acid encoding a second polypeptide having metalloregulator ArsR / SmtB activity, a fourth recombinant nucleic acid encoding a polypeptide having acyl- CoA dehydrogenase activity, Attorney Docket No.15670-0420WO1 a fifth recombinant nucleic acid encoding a polypeptide having amino acid adenylation activity, a sixth recombinant nucleic acid encoding a polypeptide having acyl carrier activity, a seventh recombinant nucleic acid encoding a polypeptide having tryptophan halogenase activity, an eighth recombinant nucleic acid encoding a first polypeptide having T1 polyketide synthase (PKS) activity, a ninth recombinant nucleic acid encoding a second polypeptide having T1PKS activity, a tenth recombinant nucleic acid encoding a third polypeptide having T1PKS activity, an eleventh recombinant nucleic acid encoding a fourth polypeptide having T1PKS activity, and a twelfth recombinant nucleic acid encoding a polypeptide having thioesterase / hydrolase activity, to produce the compound of Formula (I); and isolating the compound of Formula (I) from the culture medium. Also provided herein are methods for producing an isolated Compound 1, Compound 1a, Compound 2, or Compound 2a, where the methods include expressing, in a host cell cultured in a culture medium: a first recombinant nucleic acid encoding a first polypeptide having metalloregulator ArsR / SmtB activity, a second recombinant nucleic acid encoding a polypeptide having phosphopentetheinyl transferase activity, a third recombinant nucleic acid encoding a second polypeptide having metalloregulator ArsR / SmtB activity, a fourth recombinant nucleic acid encoding a polypeptide having acyl- CoA dehydrogenase activity, a fifth recombinant nucleic acid encoding a polypeptide having amino acid adenylation activity, a sixth recombinant nucleic acid encoding a polypeptide having acyl carrier activity, Attorney Docket No.15670-0420WO1 a seventh recombinant nucleic acid encoding a polypeptide having tryptophan halogenase activity, an eighth recombinant nucleic acid encoding a first polypeptide having T1 polyketide synthase (PKS) activity, a ninth recombinant nucleic acid encoding a second polypeptide having T1PKS activity, a tenth recombinant nucleic acid encoding a third polypeptide having T1PKS activity, an eleventh recombinant nucleic acid encoding a fourth polypeptide having T1PKS activity, and a twelfth recombinant nucleic acid encoding a polypeptide having thioesterase / hydrolase activity, to produce Compound 1, Compound 1a, Compound 2, or Compound 2a; isolating Compound 1, Compound 1a, Compound 2, or Compound 2a from the culture medium. Also provided herein are methods for preparing a composition containing a compound of Formula (I), where the methods include: culturing a population of bacteria (e.g., Streptomyces such as MAR4 Streptomyces or other idp-like BGC-containing bacteria) in media containing, for example, 10 g / L starch, 4 g / L yeast extract, 2 g / L peptone, 22 g / L instant ocean, and 0.1 g / L KBr for an appropriate length of time (e.g., seven to ten days); incubating the cultured bacteria with XAD-7 resin for an appropriate length of time (e.g., three to seven days); filtering the resin-treated bacteria, washing the filtered bacteria with water, eluting the washed bacteria with methanol, and evaporating the methanol to generate a crude extract; purifying a compound of Formula (I) using vacuum liquid chromatography and / or HPLC; and combining the compound with a carrier (e.g., a pharmaceutically acceptable carrier). Attorney Docket No.15670-0420WO1 This document also provides methods for preparing a composition containing Compound 1, Compound 1a, Compound 2, or Compound 2a, where the methods include: culturing a population of bacteria (e.g., Streptomyces such as MAR4 Streptomyces or other idp-like BGC-containing bacteria) in media containing, for example, 10 g / L starch, 4 g / L yeast extract, 2 g / L peptone, 22 g / L instant ocean, and 0.1 g / L KBr for an appropriate length of time (e.g., seven to ten days); incubating the cultured bacteria with XAD-7 resin for an appropriate length of time (e.g., three to seven days); filtering the resin-treated bacteria, washing the filtered bacteria with water, eluting the washed bacteria with methanol, and evaporating the methanol to generate a crude extract; purifying the Compound 1, Compound 1a, Compound 2, or Compound 2a using vacuum liquid chromatography and / or HPLC; and combining the compound with a carrier (e.g., a pharmaceutically acceptable carrier). In some embodiments, the MAR4 Streptomyces is strain CNY-716. In some embodiments, the methods can include culturing the population of bacteria for 10 days. In some embodiments, the purifying can include fractionating the crude extract using vacuum liquid chromatography and a step wise methanol:water (MeOH:H2O) gradient. In some embodiments, the step wise MeOH:H2O gradient can include eight fractions having ratios of: (1) 25:75 MeOH:H2O, (2) 50:50 MeOH:H2O, (3) 60:40 MeOH:H2O, (4) 70:30 MeOH:H2O, (5) 80:20 MeOH:H2O, (6) 90:10 MeOH:H2O, and (7 and 8) 100% MeOH. In some embodiments, fractions (6) and (7) can include indanopyrroles. In some embodiments, the methods can include using HPLC to purify Compound 1, Compound 1a, Compound 2, or Compound 2a from fractions (6) and (7). In some embodiments, the methods can include using HPLC to purify the compound of Formula (I) from fractions (6) and (7). In some embodiments, the carrier can be selected from the group consisting of saline solution, binding agents (e.g., polyvinylpyrrolidone or hydroxypropyl methylcellulose); fillers (e.g., lactose or dextrose and other sugars, gelatin, or calcium Attorney Docket No.15670-0420WO1 sulfate); lubricants (e.g., starch, polyethylene glycol, or sodium acetate); disintegrants (e.g., starch or sodium starch glycolate); and wetting agents (e.g., sodium lauryl sulfate). Also provided herein are methods for preparing a composition containing a compound of Formula (I), where the methods can include: expressing, in a host cell cultured in a culture medium: a first recombinant nucleic acid encoding a first polypeptide having metalloregulator ArsR / SmtB activity, a second recombinant nucleic acid encoding a polypeptide having phosphopentetheinyl transferase activity, a third recombinant nucleic acid encoding a second polypeptide having metalloregulator ArsR / SmtB activity, a fourth recombinant nucleic acid encoding a polypeptide having acyl- CoA dehydrogenase activity, a fifth recombinant nucleic acid encoding a polypeptide having amino acid adenylation activity, a sixth recombinant nucleic acid encoding a polypeptide having acyl carrier activity, a seventh recombinant nucleic acid encoding a polypeptide having tryptophan halogenase activity, an eighth recombinant nucleic acid encoding a first polypeptide having T1 polyketide synthase (PKS) activity, a ninth recombinant nucleic acid encoding a second polypeptide having T1PKS activity, a tenth recombinant nucleic acid encoding a third polypeptide having T1PKS activity, an eleventh recombinant nucleic acid encoding a fourth polypeptide having T1PKS activity, and a twelfth recombinant nucleic acid encoding a polypeptide having thioesterase / hydrolase activity, to produce the compound of Formula (I); isolating the compound of Formula (I) from the culture medium; and Attorney Docket No.15670-0420WO1 combining the compound with a carrier (e.g., a pharmaceutically acceptable carrier). Also provided herein are methods for preparing a composition containing Compound 1, Compound 1a, Compound 2, or Compound 2a, where the methods can include: expressing, in a host cell cultured in a culture medium: a first recombinant nucleic acid encoding a first polypeptide having metalloregulator ArsR / SmtB activity, a second recombinant nucleic acid encoding a polypeptide having phosphopentetheinyl transferase activity, a third recombinant nucleic acid encoding a second polypeptide having metalloregulator ArsR / SmtB activity, a fourth recombinant nucleic acid encoding a polypeptide having acyl- CoA dehydrogenase activity, a fifth recombinant nucleic acid encoding a polypeptide having amino acid adenylation activity, a sixth recombinant nucleic acid encoding a polypeptide having acyl carrier activity, a seventh recombinant nucleic acid encoding a polypeptide having tryptophan halogenase activity, an eighth recombinant nucleic acid encoding a first polypeptide having T1 polyketide synthase (PKS) activity, a ninth recombinant nucleic acid encoding a second polypeptide having T1PKS activity, a tenth recombinant nucleic acid encoding a third polypeptide having T1PKS activity, an eleventh recombinant nucleic acid encoding a fourth polypeptide having T1PKS activity, and a twelfth recombinant nucleic acid encoding a polypeptide having thioesterase / hydrolase activity, to produce Compound 1, Compound 1a, Compound 2, or Compound 2a; Attorney Docket No.15670-0420WO1 isolating Compound 1, Compound 1a, Compound 2, or Compound 2a from the culture medium; and combining the compound with a carrier (e.g., a pharmaceutically acceptable carrier). In some embodiments, the carrier can be selected from the group consisting of saline solution, binding agents (e.g., polyvinylpyrrolidone or hydroxypropyl methylcellulose); fillers (e.g., lactose or dextrose and other sugars, gelatin, or calcium sulfate); lubricants (e.g., starch, polyethylene glycol, or sodium acetate); disintegrants (e.g., starch or sodium starch glycolate); and wetting agents (e.g., sodium lauryl sulfate). Methods of Use Also provided herein are methods for using the compositions described herein. For example, this document provides methods for using a composition provided herein to kill bacteria. In some cases, a composition can contain a purified compound described herein (e.g., a compound of Formula (I)). In some cases, a composition can contain bacteria that produce a compound described herein (e.g., a compound of Formula (I)), optionally in the presence of a medium in which the bacteria were cultured. The methods can include, for example, contacting the bacteria with a composition described herein, where the composition includes an effective concentration of the compound of Formula (I). The bacteria can be Gram negative bacteria, or the bacteria can be Gram positive bacteria. In some embodiments, the bacteria can include one or more of Staphylococcus, Streptococcus, Enterococcus, Haemophilus, Escherichia, and Acinetobacter. For example, the bacteria can include one or more of Staphylococcus aureus, Enterococcus faecium, Staphylococcus epidermidis, Haemophilus influenzae, Escherichia coli, and Acinetobacter baumannii. In some cases, this document provides methods for using a composition provided herein as an insecticide. The methods can include, for example, contacting an insect (e.g., a fly, a gnat, a cabbage worm, a potato beetle, or a cotton aphid) with a composition described herein, where the composition includes an effective concentration of the compound of Formula (I). In some cases, a composition can contain a purified compound described herein (e.g., a compound of Formula (I)). In some cases, a composition can contain bacteria that produce a compound described Attorney Docket No.15670-0420WO1 herein (e.g., a compound of Formula (I)), optionally in the presence of a medium in which the bacteria were cultured. As used herein, an “effective concentration” of a compound of Formula (I) is a concentration sufficient to kill a target organism (e.g., a bacterium or an insect). In some embodiments, the effective concentration can be from about 0.5 µg / mL to about 5 µg / mL (e.g., about 0.5 µg / mL to about 1 µg / mL, from about 1 µg / mL to about 3 µg / mL, or from about 3 µg / mL to about 5 µg / mL. In some cases, the effective concentration can be greater than about 5 µg / mL (e.g., greater than about 7.5 µg / mL, greater than about 10 µg / mL, or greater than about 15 µg / mL). In some embodiments, a method provided herein can include applying to (e.g., spraying) one or more plants (e.g., one or more plants in a field of crops) with a composition provided herein. In some embodiments, a method provided herein can include spraying a marine surface with a composition provided herein. In some embodiments, a method of using a composition provided herein can be is carried out in vitro. For example, a composition containing a compound of Formula (I) can be applied to an inanimate object. In some embodiments, a method of using a composition provided herein can be carried out in vivo. For example, a composition containing a composition containing a compound of Formula (I) and a carrier (e.g., a pharmaceutically acceptable carrier) can be administered to a vertebrate. The composition can be administered by any appropriate route. For example, a composition provided herein can be administered orally, topically, by injection (e.g., subcutaneous injection, intravenous injection, intramuscular injection, or intraperitoneal injection), or any combination thereof. In some cases, a pharmaceutical composition provided herein can be administered by transmucosal or transdermal means. For transmucosal or transdermal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants include, for example, detergents, bile salts, and fusidic acid derivatives. Transmucosal administration can be accomplished through the use of nasal sprays or suppositories. EXAMPLE The invention is further described in the following example, which does not limit the scope of the invention described in the claims. Attorney Docket No.15670-0420WO1 Example 1. Paired Genome / Metabolome Mining Guides Discovery of the Antibiotic Indanopyrrole A from Marine Streptomycete Bacteria Methods and materials General experimental procedures. NMR spectra (1D and 2D) were measured at 23 °C on a JEOL ECZ spectrometer (500 MHz), equipped with a 3 mm1H{13C} room temperature probe (JEOL, Akishima, Tokyo, Japan) or on a Bruker Avance III (600 MHz) NMR spectrometer with a 5 mm1H{13C / 15N} room temperature probe (Billerica, MA).13C NMR spectrum was recorded on a Varian 500 MHz spectrometer equipped with a 5 mm1H{13C} XSens cold probe (Varan Inc., Palo Alto, CA, USA, now Agilent Technologies). NMR spectra were referenced to the solvent signals (CHD2OD, δH 3.31, CD3OD, δC49.00 ppm). LC-HRMS was performed on an Agilent 6530 Accurate-Mass QToF with ESI-source coupled with an Agilent 1260 Infinity HPLC equipped with a degasser, binary pump, autosampler, DAD detector, and a 100x4.6 mm Luna C185 µm column (Phenomenex, Torrance, CA) calibrated using the Agilent Reference Calibration Mix. HPLC was performed using Agilent’s 1100 G1312A binary pump, 1100 G1315A DAD UV / Vis detector, 1100 G1313A autosampler, and 1100 G1322A degasser (Agilent Technologies, Santa Clara, CA). Strain cultivation and metabolite extraction. All cultures were grown at 28 °C and shaken at 230 rpm with metal springs in A1 media containing potassium bromide (10 g / L starch, 4 g / L yeast extract, 2 g / L peptone, 22 g / L instant ocean, 0.1 g / L KBr). Cryogenic stocks of 40 MAR4 strains as well as lyophilized material for the two type strains purchased from the DSMZ were inoculated into 50 mL of media and one week of preculture before inoculation of 0.5 mL into fresh 50 mL media for a “second seed” culture. After five days of second seed culture, a 5 mL sample was frozen for DNA analysis and 0.5mL used to inoculate fresh media. On the fourth day of this incubation, 1 g (wet weight) of HP-20 resin was added to each flask. After three days of incubation with resin all flasks were chemically extracted with 50 mL of ethyl acetate. Water was removed from the organic layer using anhydrous Na2SO4, which was later removed by filtration. The organic layer was then dried by rotary evaporation and stored at -20°C until further analysis. Attorney Docket No.15670-0420WO1 Large-scale cultivation and extraction of CNY-716 strain. A 10 mL aliquot of small-scale pre-cultured strains (as described above) was inoculated in three 2.8 L Fernbach flasks containing 1 L of A1 medium and incubated (28 °C at 120 rpm). On day 7 and 10, aliquots (10 mL each) of the culture medium were extracted with ethyl acetate and analyzed with LCMS for indanopyrrole A production. On day 10, 20 g of activated sterile XAD-7 resin (Acros Organics, now ThermoFisher Scientific) were added to each flask and the cultures was incubated for additional 4 days under the same conditions. After a total of 14 days, the resin and the cellular material were filtered through a cheesecloth, washed with deionized H2O and eluted 4 times with 200 mL of methanol (MeOH). The solvent was then evaporated under reduced pressure to yield 2.0 g of black tar-like extract. Fractionation and Isolation. CNY-716 crude extract was fractionated using vacuum liquid chromatography (15 g of C18 material) and step wise MeOH:H2O gradient (50 mL each fraction; 25:75, 50:50, 60:40, 70:30, 80:20, 90:10 and 2 times 100% MeOH) into eight fractions LC1- 8. Fractions containing indanopyrroles (LC6-7) were further purified on HPLC (Phenomenex Kinetex C185 µm 150x4.6 mm column, isocratic ACN:H2O 68:32 0.05% FA mobile phase, 1.3 mL / min flow rate) to yield 5 mg of indanopyrrole A (1, retention time 12 min) and 0.5 mg indanopyrrole B (2, retention time 6 min). Genomic DNA Extraction. DNA extraction for the 42 MAR4 strains was performed from the 5mL frozen aliquots using the Promega Wizard Genomic DNA Purification Kit with suggested modifications for Gram-positive bacteria. DNA purity, concentrations, and size were assessed using NanoDrop, Qubit, and gel electrophoresis (ran on a 1% agarose gel). Short-read, paired-end Illumina sequencing (PE150) was performed at SeqCenter (Pittsburgh, PA). Initial genome assembly was performed by first quality filtering raw reads with the BBMap Toolkit (Work BBMap: A Fast, Accurate, Splice-Aware Aligner.2014, 3–5) followed by a preliminary assembly using SPAdes (Bankevich Journal of Computational Biology 2012, 19 (5), 455–477). All assemblies were compared for whole-genome average nucleotide identity (ANI) using fastANI (Jain Attorney Docket No.15670-0420WO1 Nat Commun 2018, 9 (1), 5114) to identify strains sharing 95% ANI. Ten representative strains from each 95% ANI clade were selected for long-read Nanopore sequencing (Oxford) and compiled with public SRA data from previously sequenced strains (N=12 Illumina, N=3 PACBIO). Data were combined for each strain to perform a hybrid assembly with unicycler (Wick PLoS Comput Biol 2017, 13 (6), 1– 22) using a kmer count 31,41,51,61,71,81,91,95,101,105,111 and “mode” determined by ANI similarity to a reference strain (i.e., “bold” with ANI=100%, “normal” with ANI>99%, “conservative” with ANI >97%). All assemblies were checked for quality, completeness, and contamination with checkM (Parks Genome Res 2015, 25 (7), 1043–1055). Biosynthetic gene clusters (BGCs) from all MAR4 genomes were predicted using antiSMASH v5 (Blin Nucleic Acids Res 2019, 47 (W1), W81–W87) and clustered into gene cluster families using BiG-SCAPE (Navarro-Muñoz Nat Chem Biol 2020, 16 (1), 60–68) with GCFs defined at 0.4 dissimilarity based on a combined metric of gene synteny, protein domain structure, and homology. MAR4 BGCs were also compared to the MIBiG 2.7 database for dereplication. Network files from BIG- SCAPE were visualized in Cytoscape. Synteny plots were generated from GBK files created by AntiSMASH using the clinker package with default parameters. Amino Acid sequences for alignments were sourced from NCBI GenBank and the AntiSMASH outputs for each BGC. Muscle5 (Edgar Nat Commun 2022, 13 (1), 6968) was used to create a stratified ensemble of alignments using the default parameters. The highest scoring alignment from this ensemble was extracted and used for active site analyses. Metabolomics and Mass Spectrometry. The dried crude extracts were resuspended to 1mg / mL in HPLC grade methanol and centrifuge filtered using 0.2 µm filters. The resuspended samples were analyzed by high performance liquid chromatography-tandem mass spectrometry, injecting 5 µL of sample into a system consisting of an Agilent 1290 HPLC coupled to an Agilent 6530 quadrupole time-of-fight (QToF) spectrometer. Parameters were set to a flow rate of 0.75 mL / min through a Kinetex C18 reversed-phase column (5 μm, 150 by 4.6 mm) under the following conditions: 0-4 min 5% acetonitrile (0.1% TFA) in water (0.1% TFA) with this first 4 minutes diverted to waste, 4-34 min: 10- Attorney Docket No.15670-0420WO1 100% acetonitrile (0.1% TFA) in water (0.1% TFA), 34-36 min 100% acetonitrile, 36-36.5 min 100-5% acetonitrile, 36.5-40 min 5% acetonitrile. MS1 data collection was done in positive and negative modes separately with a mass range of 80-1,700 m / z acquiring three spectra per second, MS2 fragmentation data was collected two scans per second with a collision energy of 30eV. The source gas temperature was 300 °C at a flow rate of 11 L per minute at 35 psig. Molecular modelling, Protein Structure and Docking Studies. 3D model of compound 1a was built in Spartan’24 V1.1.0 and minimal energy conformers were searched using molecular mechanics (CorrMMFF, ΔE <25 kJ / mol) and further optimized using DFT (Est. Density Functional ωB97X-D / 6-31G*). See Table 2A. The online version of ColabFold (colab.research.google.com / github / sokrypton / ColabFold / blob / main / AlphaFold2.ipynb) was used to generate a 3D structure from the amino acid sequence of the IdpK KS domain. Default parameters were used except the “template_mode” was changed to include the pdb70 reference library. In parallel, the 3D structure of indanopyrrole was generated based on the stereochemical predictions from the bioinformatics analysis. Both 3D models were used as input for docking analysis using AMDock. The default search parameters were used in an Autodock Vina model. Table 2A. Cartesian coordinates of Compound 1a (minimal energy conformer). 01 C 1.244078331.780454162.07580351 C 1.540729110.315816222.31235657 H 2.328439900.242767903.06836467 C 2.365929912.726400791.97212673 O 0.114069452.191024631.84312991 N 2.135398643.916148111.32757735 H 1.257301424.133490250.84226881 C 3.278294684.618096481.22735499 C 4.296614273.908849631.84194565 C 3.716841002.713903012.31391776 Cl 4.582975451.503290243.18229683 Cl 5.934399074.397026011.99572698 Attorney Docket No.15670-0420WO1 Cl 3.346975046.136631520.44273459 C 2.15285814 -0.253276080.97085104 C 2.16584070 -1.771524340.94421638 H 2.70994189 -2.220228230.11551990 C 1.53969985 -2.544895201.82874508 H 1.55117812 -3.626979351.71183068 C 0.84868193 -1.959370933.01883632 H 1.58062871 -1.907006523.84392222 C 0.35336896 -0.530887132.76730681 C -0.38242509 -0.218224604.08512112 H 0.38376324 -0.019100804.84918110 C -1.07286552 -1.574998424.42325302 H -2.14276447 -1.511106914.19780408 H -0.99099441 -1.793778705.49240137 C -0.39392300 -2.664983373.55927697 H -1.03976378 -2.961095492.72426736 H -0.15477974 -3.571008634.12417482 C -1.384730600.931774144.08593412 H -0.904184541.907628264.00596855 H -2.082582020.835708213.24587573 H -1.970589870.914328545.01249018 H -0.39230692 -0.555828631.95814987 C 1.398850240.24003854 -0.24606046 H 0.36782327 -0.11062230 -0.30368635 C 1.827940171.03360597 -1.23651606 C 0.919549541.28127745 -2.42394831 H 1.468477751.10063722 -3.35720668 H 0.075370750.58551344 -2.40329555 C 0.362358252.72121105 -2.48479565 H 1.172378733.42474098 -2.69914376 C -0.719795632.85608598 -3.56273350 H -0.304393572.60128030 -4.54257116 H -1.557568192.18143176 -3.35995962 Attorney Docket No.15670-0420WO1 H -1.102550313.88003171 -3.61117743 C -0.185760053.12617445 -1.13622549 O -1.027045782.22888020 -0.62745930 H -1.108689882.409037680.32945208 O 0.101793434.16345700 -0.56681781 C 3.141857291.77070600 -1.26099366 H 3.656595281.60752095 -2.21616840 H 2.987630072.85301693 -1.16235781 H 3.814516781.47262028 -0.45435235 H 3.194564010.084309600.91528622 121.041.052.0 231.0141.0211.0 3 461.0102.0 5 671.081.0 7 892.0131.0 9101.0121.0 10111.0 11 12 13 14151.0351.0551.0 15161.0172.0 16 17181.0191.0 18 19201.0211.0271.0 20 21221.0341.0 22231.0241.0301.0 Attorney Docket No.15670-0420WO1 23 24251.0261.0271.0 25 26 27281.0291.0 28 29 30311.0321.0331.0 31 32 33 34 35361.0372.0 36 37381.0511.0 38391.0401.0411.0 39 40 41421.0431.0471.0 42 43441.0451.0461.0 44 45 46 47481.0502.0 48491.0 49 50 51521.0531.0541.0 52 53 54 55 Attorney Docket No.15670-0420WO1 Antibacterial testing, Initial Screening. 12.8 µg of Compound 1a were used to prepare ten solutions by half-serial dilutions (from 128 µg / mL to 0.25 µg / mL) in a 96-well plate using sterile medium (Muller-Hinton broth; 50 uL of each solution per well). An E. coli LptD 4213 inoculum (50 µL solution) was added to wells containing the different concentrations of 1 to reach a final concentration of 2e5 CFU / mL. Due to the 1:1 dilution, the range of final tested concentrations ranged from 64 µg / mL to 0.125 µg / mL. After the incubation for 18 hours at 37°C, the well with the lowest concentration of compound that did not exhibit microbial growth (i.e., similar to chloramphenicol controls) was determined to be the MIC. Compound 1a inhibited the growth of E. coli LptD 4213 at 64 µg / mL, 32 µg / mL, 16 µg / mL, 8 µg / mL, and 4 µg / mL, but not at 2 µg / mL or at lower concentrations. Therefore, the MIC of Compound 1a was determined to be 4 µg / mL. Minimal Inhibitory Concentration (MIC) assay with clinical isolates. MIC values were determined using broth microdilution in accordance with the Clinical Laboratory Standards Institute (CLSI) guidelines using cation-adjusted Mueller Hinton Broth (MHB) with minor modifications. Briefly, bacteria were grown to mid-log phase (OD600nm = 0.4) at 37°C while shaking except GAS which was grown under static condition. Bacterial cells were then centrifuged, washed, and diluted in PBS to obtain 2×106cfu / mL, and 10 μL was added to individual wells of a 96-well plate containing 170 μL MHB. Serial dilutions of indanopyrroles A and B starting at 32 μg / mL or 16 μg / mL, respectively, were made in a separate plate, 20 μL of the compound was then added to the test plate. The plates were sealed with parafilm and incubated at 37°C for 24 h. The turbidity of each plate was measured at OD600nmusing the EnSpire Alpha plate reader. MIC was defined as the lowest concentration of the drugs that inhibited bacterial growth. Cell Viability Assay. A549 cells were seeded in 24 well plates (Corning, United States) at 2x105cells / well. Cells were left untreated or treated with 16, 32 and 128 μg / mL of indanopyrrole A, or with corresponding amounts of the H2O:DMSO (1:2) solvent Attorney Docket No.15670-0420WO1 vehicle as negative control. As positive control, A549 cells were lysed with Triton X- 100. Cell culture supernatants were collected at two time points 2 and 24 hrs. Cellular cytotoxicity was assessed by measuring the levels of lactate dehydrogenase (LDH; Promega, United States) released by host cell into supernatant. The percentage of cell death was calculated after subtracting the levels found in untreated control cells and dividing by the levels in a positive control of cells treated with a lysis solution (Triton X-100). Results Isolation and structure elucidation. A search for novel, halogenated products from 42 MAR4 strains using HR- ESI-TOF-MS led to the detection of a compound with an m / z of 458.1060 [M+H]+and an isotopic pattern characteristic of a trichlorinated molecule in the culture extract of seven strains (FIG.3). A Dictionary of Natural Products search retrieved no matches, suggesting it represented a new compound. Among the producing strains, the highest production was detected in strain CNY-716. Larger scale (3 L) cultivation yielded 5 mg of the target compound. Interestingly, in the large-scale cultures this compound was only observed after prolonged fermentation (see Methods) and the addition of XAD-7 resin to the culture broth (FIG.5). The molecular formula (MF) of Compound 1a was calculated from the accurate mass (458.1060 [M+H]+) as C22H26Cl3NO3with nine degrees of unsaturation. NMR experiments (1H,13C, COSY, HSQC and HMBC) in CD3OD led to the unambiguous elucidation of the planar structure (Table 3A). The proton spectrum showed the presence of two methyl doublets (CH3-20 and CH3-22; δH 0.99, J = 6.1 Hz and 0.98, J = 6.8 Hz) and one methyl singlet (CH3-21; δH 1.31) attached to a C=C double bond. Additionally, three sp2resonances at 5.06 (H-5, d, J = 10.3 Hz), 5.33 (H-7, dt, J = 3.4, 9.7 Hz), and 5.84 ppm (H-8, dt, J = 1.8, 9.7 Hz) accounted for two C=C double bonds. An extensive spin system reaching from H-5 to H-14 was evident in the1H-1H COSY experiment. This established the tetrahydroindane core of the molecule (FIG.6A) and located the methyl group at C-12 and the other two substituents at the positions C-6 and C-14.1H-13C long range correlations (HMBC) from the methyl protons H3-21 to C-3, C-4, and C-5 and from H3-22 to the carboxylic acid carbonyl C-1 (δC 182.7 ppm), C-2, and C-3 established the substituent at C-6. Attorney Docket No.15670-0420WO1 This substructure accounted for 17 carbons, 25 protons, two oxygens, and five degrees of unsaturation. The remaining C5HCl3NO moiety is in agreement with a trichloropyrrole connected via a carbonyl to C-14 (fragment m / z 195.9127 in the MS / MS spectrum FIG.4) as reported for related indanomycin-type compounds (Larsen et al. J Antibiot (Tokyo) 1988, 41 (9), 1170–1177; Miao et al. Tetrahedron Lett 1995, 36 (32), 5699–5702; Izumikawa et al. J Antibiot (Tokyo) 2008, 61 (5), 326– 329; and Beloeil et al. J Org Chem 1984, 49 (10), 1797–1800. The UV maximum at 300 nm provides further support for a pyrrole moiety. HMBC correlations from H-14 to the carbonyl C-15 and C-16 established the connection of the trichloropyrrole moiety to the indane core.13C NMR experiment provided δC chemical shifts for the remaining chlorinated carbons (C-17, C-18 and C-19) that were unassigned by indirect detection secured the planar structure of a new compound designated herein as Compound 1a. The relative configuration of the indane core was established with NOESY correlations and is analogous to the reported pyrroloketoindanes (Indanomycin (3), Cafamycin (4), 16-Deethylindanomycin (5), Homoindanomycin (6), Stawamycin (7), and JBIR-11 (8)). The E Δ4C=C double bond geometry was evident from the13C chemical shift of the CH3-21 (15.7 ppm). Absolute configurations at C-2 and C-12 were predicted bioinformatically to be 2R and 2S based on an analysis of the candidate biosynthetic gene cluster (see below). Absolute configuration for compound 1a was based on bioinformatic prediction. Table 3A. NMR data of compound 1a. Attorney Docket No.15670-0420WO1 b 2.28, dd (5.7, C-1, C-2, C-4, 13.7) H-2, H-5 C-5, C-22 , Attorney Docket No.15670-0420WO1 22 16.8, 0.98, d (6.8) H-2 C-1, C-2, C-3 CH3 bMultiplicities determined by HSQC. During the isolation of Compound 1a, 0.5 mg of a minor compound was obtained that shared the same chromophore. MS analyses (m / z [M+H]+424.1451, calculated MF C22H27Cl2NO3, pyrrole containing MS / MS fragment m / z 161.9527 calcd. MF = C5H2Cl2NO, FIG.7 and FIG.8) indicated that it is a dichloropyrrole analog of Compound 1a that is designated herein as compound 2a. To infer the position of the dechlorination,1H, HSQC, and HMBC NMR spectra were recorded using a 600 MHz NMR and 5 mm cryoprobe (Table 3B). As expected, the1H spectrum was almost identical with that of Compound 1a, except for an additional sharp singlet at 7.04 ppm, the upfield shift of H-6 and H-14 resonances (from 3.65 to 3.50 and 3.88 to 3.49 ppm, respectively), and the slight upfield shift of H3-20 resonance from 0.99 to 0.92 ppm. In the HMBC spectrum of compound 2a, a long- range correlation was observed from the proton resonance at 7.04 ppm to the C-15 carbonyl, which establishes the hydrogen placement on C-17 and the structure of compound 2a as a 17-deschloro derivative of Compound 1a. Absolute configuration for compound 2a was based on bioinformatic prediction. Table 3B. NMR data of compound 2a. Attorney Docket No.15670-0420WO1 C-1, C-2, C-4, C-5, C-21, C-22 3 HSQC, HMBC).bMultiplicities determined by HSQC. Identification of the candidate indanopyrrole (idp) bgc. Based on biosynthetic precedent for the pyrrole containing products indanomycin (3) (Li ChemBioChem 2009, 10 (6), 1064–1072), chlorizidine Attorney Docket No.15670-0420WO1 (Mantovani J Am Chem Soc 2013, 135 (48), 18032–18035), armeniaspirol (Fu ChemBioChem 2019, 20 (6), 764–769), and marinopyrrole (Yamanaka J Am Chem Soc 2012, 134 (30), 12434–12437), it was proposed that indanopyrrole biosynthesis is initiated using a proline derived di- or trichloropyrrole starter unit. Given this, a DIAMOND BLAST (Buchfink Nat Methods 2021, 18 (4), 366–368) database containing 42 MAR4 genomes was created using cblaster (Gilchrist Bioinformatics Advances 2021, 1 (1), 1–10). Using this database, the proline adenyltransferase (IdmJ) and prolyl-Carrier protein dehydrogenase (IdmI) sequences from the indanomycin (idm) BGC (MIBiG #: BGC0000079) (Terlouw Nucleic Acids Res 2023, 51 (D1), D603–D610) were used as queries to detect candidate indanopyrrole BGCs. This analysis returned 33 gene cluster hits within 25 MAR4 genomes. While some strains had as many as three BGCs containing the pyrrole biosynthetic hooks, only one BGC was shared by all seven indanopyrrole producing strains and shared the most genes (39%) with idm. Using this pattern-based genome mining approach (Duncan Chem Biol 2015, 22 (4), 460–471), this BGC was identified as the top candidate for indanopyrrole biosynthesis and given the name idp (FIG.1A and FIG.9). From this analysis of 42 MAR4 genomes, 15 strains contained full-length BGCs, and an additional five strains contained partial BGCs located on the edges of assembled contigs (FIG.9). While only seven strains were found to produce indanopyrrole, two producing strains were found to contain these partial BGCs and there is little genetic evidence to suggest that any of these BGCs is nonfunctional. At this time, it is not understood why production was detected in so few of the strains containing the idp BGC. A comparison of the idp and idm BGCs reveals structural differences between their small molecule products (FIG.1A and FIG.1B). Both BGCs contain genes encoding proline adenyltransferases (idpE / idmJ), proline carrier proteins (idpF / idmK), and dehydrogenases (idpD / idmI) to account for the generation of the pyrrole moieties (FIG.1C). Idp then diverges by the presence of a halogenase gene annotated as a tryptophan halogenase (idpG), the product of which likely accounts for the tri- or dichlorinated pyrrole moieties observed in compound 1a and compound 2a and is shares homology with halogenase genes from other chlorinated pyrrole containing natural product BGCs (Mantovani et al. J Am Chem Soc 2013, 135 (48), 18032– 18035; Fu et al. ChemBioChem 2019, 20 (6), 764–769.; and Purdy et al. Am Chem Attorney Docket No.15670-0420WO1 Soc 2021, 143 (10), 3682–3686. The chlorinated pyrrole generated from idpD-G is then used as a starter unit for seven polyketide extensions encoded by three T1PKS genes (idpH-J). Notably, a NaPDoS2 (Ziemert et al. PLoS One 2012, 7 (3), e34064; and Klau et al. J Biol Chem 2022, 298 (10), 102480) analysis of the module 1 ketosynthase (KS) domain within IdpH indicates that it forms a clade with other pyrrole accepting KSs, further supporting the functional prediction for the starter unit (FIG.10A). Following starter unit selection, the AT domains associated with modules two, six, and seven are predicted to select for methylmalonyl-CoA. Module two contains an A2-type ketoreductase (KR) domain based on the conserved tryptophan and histidine residues and as such can be bioinformatically predicted to install 2S, 3S configuration at this position (FIG.11). Module 3 (idpH) contains the full suite of domains to generate the alkane while modules 4-6 (idpI) contain KR and dehydratase (DH) domains to afford a conjugated triene. Module 7 contains the full suite of domains to generate a branched alkane with bioinformatically predicted R stereochemistry based on the lack of a conserved tyrosine residue in the active site of the idpJ enoylreductase (ER) domain (Kwan Molecules 2011, 16 (7), 6092–6115) (FIG.12). The final T1PKS module (module 8, idpK) consists of a KS and an acyltransferase (AT) domain and was observed in all idp BGCs except one partial BGC which was truncated before this gene. This unusual organization is observed in all idpK genes detected and resembles the terminal PKS module in idm, which differs by also containing a terminal cyclase domain. Another difference with idm is that the AT / KS domains in the terminal module of all idpK genes lack the active site residues required for selection / loading and decarboxylative condensation, respectively (FIG. 13 and FIG.14). The inability of this module to support chain extension is supported by the structures of compound 1a and compound 2a. A stand-alone thioesterase (TE) domain (idpL) located immediately after idpK is homologous to idmA, which was presumed to be associated with chain release from the megasynthase during indanomycin (3) biosynthesis (Keatinge-Clay Chem Rev 2017, 117 (8), 5334–5366). However, an analysis using the THYME thioesterase database of the idpL and idmA genes places them in the TE18 family of “editing” type II TEs, which remove prematurely decarboxylated extender units, stalled intermediates, or improperly edited Attorney Docket No.15670-0420WO1 CoA-bound starter units (Cantu Protein Science 2010, 19 (7), 1281–1295 and Cantu Nucleic Acids Res 2011, 39 (Database), D342–D346). Thus, it does not appear that idpL plays a role in chain release. In the case of indanomycin, offloading was proposed to involve the terminal cyclase domain (Li ChemBioChem 2009, 10 (6), 1064–1072), however the lack of this domain in idpK suggests either a different mechanism for compound 1a and compound 2a or that the cyclase is not involved (FIG.15). While antiSMASH calls a larger BGC, manual analyses have led us to propose that the idp BGC is best represented by idpA-idpL. As in indanomycin biosynthesis, questions remain about how the linear precursor predicted from the BGC is offloaded and cyclized to yield the final pyrroloketoindane products. Indane ring formation. Further comparison of the idm and idp BGCs and their products provides insight into the formation of the indane ring. In the case of indanomycin (3), it was suggested that idmH is an indane cyclase, however knockout experiments lowered but did not abolish compound production (Rommel Org Lett 2011, 13 (10), 2536–2539) and molecular modelling using the crystal structure did not reveal the potential for enzymatic activity (Drulyte IUCrJ 2019, 6 (6), 1120–1133). Notably, only one indanopyrrole producing MAR4 strain (CNY-716) contained an idmH homolog (36% amino acid similarity), and it was not located within any of the BGCs identified in that genome. Thus, the idmH mediated mechanism of indane ring formation proposed for indanomycin does not apply to indanopyrrole. While several idp open reading frames (orfs) could account for indane ring formation, it is intriguing to consider that the conserved KS domain associated with the non-elongating, terminal PKS module in idm and all idp gene clusters is involved. KS functional diversification is not uncommon as was recently shown in salinosporamide A biosynthesis where a non- elongating, terminal domain catalyzed intramolecular carbon-carbon bond formation to yield the cyclized end product (Bauman Nat Chem Biol 2022, 18 (5), 538–546). Phylogenetic analysis of the terminal idpK KS domain places it in a clade that includes the homolog from indanomycin biosynthesis (Jiang Appl Environ Microbiol 2012, 78 (4), 994–1003) (FIG.10) suggesting they are functionally related. Interestingly, a dehydration step was proposed in the second PKS module of idm that was not accounted for in the BGC (Li ChemBioChem 2009, 10 (6), 1064–1072) This Attorney Docket No.15670-0420WO1 dehydration was predicted to generate the alkene dienophile required for indane ring formation via a Diels-Alder [4+2] cycloaddition reaction (Li ChemBioChem 2009, 10 (6), 1064–1072; Roush J Org Chem 1981, 46 (7), 1509–1511; Rousch Tetrahedron Lett 1982, 23 (47), 4879–4882; Roush J Org Chem 1984, 49 (18), 3429–3432; and Stocking Angewandte Chemie 2003, 115 (27), 3186–3223). A similar dehydration is predicted for the indanopyrroles and the hydroxy group generated by module 2 (FIG. 1). It is interesting to speculate that the terminal KS domains observed in both idm and idp encode the cryptic dehydration step needed for the predicted cycloaddition reaction. To address the potential neofunctionalization of the IdpK KS domain, its 3D structure was modelled using the open-source implementation of AlphaFold (Jumper Nature 2021, 596 (7873), 583–589) in ColabFold (Mirdita Nat Methods 2022, 19 (6), 679–682). The model showed strong structural homology with the crystal structure of 6-deoxyerythronolide B synthase (DEBS) with the active site residues collocated within a substrate binding pocket (FIG.16A). Molecular docking studies using compound 1a and the AMDock suite (Valdés-Tresanco Biol Direct 2020, 15 (1), 12) showed that the final molecule fits within the predicted substrate binding pocket of the IdpK KS. In this model, the carboxylic acid moiety of indanopyrrole A is adjacent to active site cysteine-167. This position is homologous to DEBS cysteine-211, which forms a thioester bond with the polyketide intermediate generated by the preceding PKS module (FIG.16A inset). The shape of the substrate binding pocket conforms to the shape of indanopyrrole A suggesting that it promotes a conformational change in the linear precursor that facilitates a Diels-Alder reaction (FIG.16A, inset). In support of this, the spatial orientation aligns active site histidine-302 above C-14 in the indanomycin structure. The location of this carbon alpha to the carbonyl group could allow the active site histidine to abstract a hydrogen and initiate a cascade reaction that ends with the elimination of water from the C-13 hydroxy group thus accounting for the cryptic dehydration step (FIG.16B). While speculative, if this dehydratase activity can be established, it would support a new mechanism for indane ring formation in indanopyrroles and indanomycin. Attorney Docket No.15670-0420WO1 Gene cluster and metabolite distribution. To more broadly explore idp and idm distributions, the respective adenyltransferase (idpE / idmJ) and proline dehydrogenase (idpD / idmJ) genes and cblaster were used to remotely query the NCBI nr database (Sayers Nucleic Acids Res 2022, 50 (D1), D20–D26), which returned 3,283 and 3,198 hits, respectively. The results were filtered to include only those hits that contained at least one gene with >70% homology to a PKS gene within the query BGCs. The results were combined, and duplicates removed to yield 40 BGCs, which were manually assigned to seven BGC groups and nine singleton BGCs based on gene synteny (FIG.17). AntiSMASH analyses revealed top matches with BGCs associated with indanopyrrole, indanomycin, nargenicin, and calcimycin production along with three BGCs with no known product (FIG.17). Among the BGCs positively identified as idm three complete BGCs were detected in Streptomyces albireticuli strains (JAJQQR010000001.1, JAJQQQ010000001.1, JAJQQS010000003.1) (FIG.2) and all three lacked the terminal cyclase domain in the indanomycin BGC (FIG.15). Additionally, two putative fragmented idm BGCs were detected on contig edges in S. ureilyticus (NZ_JAAKZX010000175.1) and S. coffeae (NZ_JAERRF010000046.1). This analysis returned only one full-length idp BGC which was observed in Micromonospora sp. WMMC 250 (NZ_JAPZBJ010000002.1) (FIG.2). A putative fragmented idp BGC was also identified on a contig edge in the genome of Streptomyces sedi JCM 16909 (VDGT01000017.1). The Mass Spectrometry Search Tool (Wang Nat Biotechnol 2020, 38 (1), 23– 26) (MASST) within the Global Natural Products Social Molecular Networking (Wang Nat Biotechnol 2016, 34 (8), 828–837) (GNPS) platform was then used to search for the MS / MS spectrum of indanopyrrole A within public datasets. After detecting no hits using the default parameters, the minimum cosine score was lowered to 0.6 and the minimum matched fragments to 2 and detected 71 hits when allowing for analog searching. Upon manual inspection, none of the m / z values or fragmentation spectra from these hits matched indanopyrrole. The lack of any significant matches among 2,709 public datasets highlights the rarity of the indanopyrroles. Attorney Docket No.15670-0420WO1 Bioactivity. Initial bioactivity testing of indanopyrrole against membrane-deficient Escherichia coli lptD4213 (Nonejuie Proceedings of the National Academy of Sciences 2013, 110 (40), 16169–16174) showed a minimum inhibitory concentration (MIC) of 4 µg / mL (Table 3C). Subsequent testing against a panel of Gram positive and negative organisms showed that indanopyrrole was consistently active against the clinically relevant Gram-positive pathogens methicillin-resistant Staphylococcus aureus TCH1516 (MIC = 2 µg / mL), group A Streptococcus M1T1 (4 µg / mL), vancomycin-resistant Enterococcus faecium DAPS (2 µg / mL), and methicillin- resistant Staphylococcus epidermis (4 µg / mL) (Table 1). Notably, compound 1a was identified as the first pyrroloketoindane product to show activity against Gram- negative organisms with 1-2 µg / mL activities against Haemophilus influenzae (Table 1). Notably, compound 2a was found to be inactive at any of the concentrations tested, underscoring the importance of halogens to the activity of these molecules. The cytotoxicity of compound 1a was tested using a lactate dehydrogenase (LDH) A549 cell line-based viability assay. Cytotoxic effects were observed 16 µg / mL after 24 hours of exposure (FIG.18) indicating a “therapeutic index” of 4-8 for strains and cell lines tested. Table 3C. Antibacterial minimum inhibitory concentrations of indanopyrrole A and B. N.T. = Not Tested Strains tested Gram + / - Indanopyrrole A Indanopyrrole B Attorney Docket No.15670-0420WO1 Acinetobacter baumannii - >32 μg / mL N.T. 5075 OTHER EMBODIMENTS It is to be understood that while the invention has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.

Claims

Attorney Docket No.15670-0420WO1 WHAT IS CLAIMED IS:

1. A composition comprising a pharmaceutically acceptable carrier and an isolated and / or purified compound of Formula (I): or a pharmaceuticallywherein R1, R2, and R3are each independently H or halogen; and R4, R5, R6, and R7are each independently H, -CH3, and -CH2CH3; wherein the pharmaceutically acceptable carrier is not water.

2. The composition of claim 1, wherein the compound of Formula (I) is a compound of Formula (Ia):or a pharmaceutically acceptable salt thereof.

3. The composition of claim 1 or claim 2, or a pharmaceutically acceptable salt thereof, wherein R1is H.

4. The composition of claim 1 or claim 2, or a pharmaceutically acceptable salt thereof, wherein R1is -Cl.Attorney Docket No.15670-0420WO1 5. The composition of any one of claims 1-4, or a pharmaceutically acceptable salt thereof, wherein R2is H.

6. The composition of any one of claims 1-4, or a pharmaceutically acceptable salt thereof, wherein R2is -Cl.

7. The composition of any one 1-6, or a pharmaceutically acceptable salt thereof, wherein R3is H.

8. The composition of any one of claims 1-6, or a pharmaceutically acceptable salt thereof, wherein R3is -Cl.

9. The composition of any one of claims 1, 2, 4, 6, and 8, or a pharmaceutically acceptable salt thereof, wherein R1is -Cl, R2is -Cl, and R3is -Cl.

10. The composition of any one of claims 1-3, 6, and 8, or a pharmaceutically acceptable salt thereof, wherein R1is H, R2is -Cl, and R3is -Cl.

11. The composition of any one of claims 1-10, or a pharmaceutically acceptable salt thereof, wherein R4is -CH3.

12. The composition of any one of claims 1-11, or a pharmaceutically acceptable salt thereof, wherein R5is -CH3.

13. The composition of any one of claims 1-12, or a pharmaceutically acceptable salt thereof, wherein R6is -CH3.

14. The composition of any one of claims 1-13, or a pharmaceutically acceptable salt thereof, wherein R7is H.

15. The composition of claim 1, wherein the compound of Formula (I) is Compound 1 or Compound 2:Attorney Docket No.15670-0420WO1 orof Formula (I) is Compound 1a or Compound 2a: or17. The composition of claim 1, wherein the compound of Formula (I) is Compound 1aAttorney Docket No.15670-0420WO1 (Compound 1a) of thereof.

18. The composition of claim 1, wherein the compound of Formula (I) is Compound 2a (Compound 2a)of thereof.

19. The composition of any one of claims 1 to 18, wherein the pharmaceutically acceptable carrier is selected from the group consisting of saline solution, binding agents, fillers, lubricants, disintegrants, and wetting agents.

20. An article of manufacture comprising a composition of any one of claims 1- 19, wherein the article of manufacture optionally comprises instructions for use of the composition as an antibiotic and / or an insecticide.

21. A method for producing an isolated and purified Compound 1, Compound 1a, Compound 2, or Compound 2a: ,Attorney Docket No.15670-0420WO1 orculturing a population of MAR4 Streptomyces or other idp-like BGC- containing bacteria in media comprising 10 g / L starch, 4 g / L yeast extract, 2 g / L peptone, 22 g / L instant ocean, and 0.1 g / L KBr for seven to ten days; incubating the cultured bacteria with XAD-7 resin for three to seven days; filtering the resin-treated bacteria, washing the filtered bacteria with water, eluting the washed bacteria with methanol, and evaporating the methanol to generate a crude extract; and purifying Compound 1, Compound 1a, Compound 2, or Compound 2a using vacuum liquid chromatography and / or high-performance liquid chromatography (HPLC).

22. The method of claim 21, wherein the bacteria is strain CNY-716 of MAR4 Streptomyces.Attorney Docket No.15670-0420WO1 23. The method of claim 21 or claim 22, comprising culturing the population of bacteria for 10 days.

24. The method of any one of claims 21-23, wherein the purifying comprises fractionating crude extract using vacuum liquid chromatography and a step wise methanol:water (MeOH:H2O) gradient.

25. The method of claim 24, wherein the step wise MeOH:H2O gradient comprises eight fractions having ratios of: (1) 25:75 MeOH:H2O, (2) 50:50 MeOH:H2O, (3) 60:40 MeOH:H2O, (4) 70:30 MeOH:H2O, (5) 80:20 MeOH:H2O, (6) 90:10 MeOH:H2O, and (7 and 8) 100% MeOH.

26. The method of claim 25, wherein fractions (6) and (7) comprise indanopyrroles.

27. The method of claim 26, comprising using HPLC to purify Compound 1, Compound 1a, Compound 2, or Compound 2a from fractions (6) and (7).

28. A method for producing an isolated Compound 1, Compound 1a, Compound 2, or Compound 2a: , ,Attorney Docket No.15670-0420WO1 ora first recombinant nucleic acid encoding a first polypeptide having metalloregulator ArsR / SmtB activity, a second recombinant nucleic acid encoding a polypeptide having phosphopentetheinyl transferase activity, a third recombinant nucleic acid encoding a second polypeptide having metalloregulator ArsR / SmtB activity, a fourth recombinant nucleic acid encoding a polypeptide having acyl- CoA dehydrogenase activity, a fifth recombinant nucleic acid encoding a polypeptide having amino acid adenylation activity, a sixth recombinant nucleic acid encoding a polypeptide having acyl carrier activity, a seventh recombinant nucleic acid encoding a polypeptide having tryptophan halogenase activity, an eighth recombinant nucleic acid encoding a first polypeptide having T1 polyketide synthase (PKS) activity, a ninth recombinant nucleic acid encoding a second polypeptide having T1PKS activity, a tenth recombinant nucleic acid encoding a third polypeptide having T1PKS activity,Attorney Docket No.15670-0420WO1 an eleventh recombinant nucleic acid encoding a fourth polypeptide having T1PKS activity, and a twelfth recombinant nucleic acid encoding a polypeptide having thioesterase / hydrolase activity, to produce Compound 1, Compound 1a, Compound 2, or Compound 2a; isolating Compound 1, Compound 1a, Compound 2, or Compound 2a from the culture medium.

29. A method for preparing a composition comprising Compound 1, Compound 1a, Compound 2, or Compound 2a: orAttorney Docket No.15670-0420WO1 (Compound 2a)culturing a population of MAR4 Streptomyces bacteria in media comprising 10 g / L starch, 4 g / L yeast extract, 2 g / L peptone, 22 g / L instant ocean, and 0.1 g / L KBr for seven to ten days; incubating the cultured bacteria with XAD-7 resin for three to seven days; filtering the resin-treated bacteria, washing the filtered bacteria with water, eluting the washed bacteria with methanol, and evaporating the methanol to generate a crude extract; purifying the Compound 1, Compound 1a, Compound 2, or Compound 2a using vacuum liquid chromatography and / or high-performance liquid chromatography (HPLC); and combining the compound with a pharmaceutically acceptable carrier.

30. The method of claim 29, wherein the MAR4 Streptomyces is strain CNY-716.

31. The method of claim 29 or claim 30, comprising culturing the population of bacteria for 10 days.

32. The method of any one of claims 29-31, wherein the purifying comprises fractionating crude extract using vacuum liquid chromatography and a step wise methanol:water (MeOH:H2O) gradient.

33. The method of claim 32, wherein the step wise MeOH:H2O gradient comprises eight fractions having ratios of: (1) 25:75 MeOH:H2O, (2) 50:50 MeOH:H2O, (3) 60:40 MeOH:H2O, (4) 70:30 MeOH:H2O, (5) 80:20 MeOH:H2O, (6) 90:10 MeOH:H2O, and (7 and 8) 100% MeOH.

34. The method of claim 33, wherein fractions (6) and (7) comprise indanopyrroles.Attorney Docket No.15670-0420WO1 35. The method of claim 34, comprising using HPLC to purify Compound 1, Compound 1a, Compound 2, or Compound 2a from fractions (6) and (7).

36. The method of any one of claims 29-35, wherein the pharmaceutically acceptable carrier is selected from the group consisting of saline solution, binding agents, fillers, lubricants, disintegrants, and wetting agents.

37. A method for preparing a composition comprising Compound 1, Compound 1a, Compound 2, or Compound 2a: orexpressing, in a host cell cultured in a culture medium:Attorney Docket No.15670-0420WO1 a first recombinant nucleic acid encoding a first polypeptide having metalloregulator ArsR / SmtB activity, a second recombinant nucleic acid encoding a polypeptide having phosphopentetheinyl transferase activity, a third recombinant nucleic acid encoding a second polypeptide having metalloregulator ArsR / SmtB activity, a fourth recombinant nucleic acid encoding a polypeptide having acyl- CoA dehydrogenase activity, a fifth recombinant nucleic acid encoding a polypeptide having amino acid adenylation activity, a sixth recombinant nucleic acid encoding a polypeptide having acyl carrier activity, a seventh recombinant nucleic acid encoding a polypeptide having tryptophan halogenase activity, an eighth recombinant nucleic acid encoding a first polypeptide having T1 polyketide synthase (PKS) activity, a ninth recombinant nucleic acid encoding a second polypeptide having T1PKS activity, a tenth recombinant nucleic acid encoding a third polypeptide having T1PKS activity, an eleventh recombinant nucleic acid encoding a fourth polypeptide having T1PKS activity, and a twelfth recombinant nucleic acid encoding a polypeptide having thioesterase / hydrolase activity, to produce Compound 1, Compound 1a, Compound 2, or Compound 2a; isolating Compound 1, Compound 1a, Compound 2, or Compound 2a from the culture medium; and combining the compound with a pharmaceutically acceptable carrier.

38. The method of claim 37, wherein the pharmaceutically acceptable carrier is selected from the group consisting of saline solution, binding agents, fillers, lubricants, disintegrants , and wetting agents.Attorney Docket No.15670-0420WO1 39. A method for killing bacteria, comprising contacting the bacteria with a composition of any one of claims 1-19, wherein the composition comprises an effective concentration of the compound of Formula (I).

40. The method of claim 39, wherein the bacteria comprise Gram negative bacteria.

41. The method of claim 39, wherein the bacteria comprise Gram positive bacteria.

42. The method of claim 39, wherein the bacteria comprise one or more of Staphylococcus, Streptococcus, Enterococcus, Haemophilus, Escherichia, and Acinetobacter.

43. The method of claim 39, wherein the bacteria comprise one or more of Staphylococcus aureus, Enterococcus faecium, Staphylococcus epidermidis, Haemophilus influenzae, Escherichia coli, and Acinetobacter baumannii.

44. The method of any one of claims 39-43, wherein the effective concentration is about 0.5 µg / mL to about 5 µg / mL.

45. The method of any one of claims 39-43, wherein the effective concentration is greater than about 15 µg / mL.

46. The method of any one of claims 39-45, wherein the method is carried out in vitro.

47. The method of any one of claims 39-46, wherein the method is carried out in vivo.

48. A method for killing an insect comprising contacting the insect with a composition of any one of claims 1-19, wherein the composition comprises an effective concentration of the compound of Formula (I).

49. The method of claim 48, wherein the insect is a fly, a gnat, a cabbage worm, a potato beetle, or a cotton aphid).Attorney Docket No.15670-0420WO1 50. The method of claim 48 or 49, wherein the effective concentration is about 0.5 µg / mL to about 5 µg / mL.

51. The method of claim 48 or 49, wherein the effective concentration is greater than about 15 µg / mL.

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