RESUMO
Fungi shape the diversity of life. Characterizing the evolution of fungi is critical to understanding symbiotic associations across kingdoms. In this study, we investigate the genomic and metabolomic diversity of the genus Escovopsis, a specialized parasite of fungus-growing ant gardens. Based on 25 high-quality draft genomes, we show that Escovopsis forms a monophyletic group arising from a mycoparasitic fungal ancestor 61.82 million years ago (Mya). Across the evolutionary history of fungus-growing ants, the dates of origin of most clades of Escovopsis correspond to the dates of origin of the fungus-growing ants whose gardens they parasitize. We reveal that genome reduction, determined by both genomic sequencing and flow cytometry, is a consistent feature across the genus Escovopsis, largely occurring in coding regions, specifically in the form of gene loss and reductions in copy numbers of genes. All functional gene categories have reduced copy numbers, but resistance and virulence genes maintain functional diversity. Biosynthetic gene clusters (BGCs) contribute to phylogenetic differences among Escovopsis spp., and sister taxa in the Hypocreaceae. The phylogenetic patterns of co-diversification among BGCs are similarly exhibited across mass spectrometry analyses of the metabolomes of Escovopsis and their sister taxa. Taken together, our results indicate that Escovopsis spp. evolved unique genomic repertoires to specialize on the fungus-growing ant-microbe symbiosis.
Assuntos
Formigas , Hypocreales , Parasitos , Animais , Formigas/genética , Formigas/microbiologia , Filogenia , Simbiose/genética , Hypocreales/genéticaRESUMO
Although microbial genomes harbor an abundance of biosynthetic gene clusters, there remain substantial technological gaps that impair the direct correlation of newly discovered gene clusters and their corresponding secondary metabolite products. As an example of one approach designed to minimize or bridge such gaps, we employed hierarchical clustering analysis and principal component analysis (hcapca, whose sole input is MS data) to prioritize 109 marine Micromonospora strains and ultimately identify novel strain WMMB482 as a candidate for in-depth "metabologenomics" analysis following its prioritization. Highlighting the power of current MS-based technologies, not only did hcapca enable the discovery of one new, nonribosomal peptide bearing an incredible diversity of unique functional groups, but metabolomics for WMMB482 unveiled 16 additional congeners via the application of Global Natural Product Social molecular networking (GNPS), herein named ecteinamines A-Q (1-17). The ecteinamines possess an unprecedented skeleton housing a host of uncommon functionalities including a menaquinone pathway-derived 2-naphthoate moiety, 4-methyloxazoline, the first example of a naturally occurring Ψ[CH2NH] "reduced amide", a methylsulfinyl moiety, and a d-cysteinyl residue that appears to derive from a unique noncanonical epimerase domain. Extensive in silico analysis of the ecteinamine (ect) biosynthetic gene cluster and stable isotope-feeding experiments helped illuminate the novel enzymology driving ecteinamine assembly as well the role of cluster collaborations or "duets" in producing such structurally complex agents. Finally, ecteinamines were found to bind nickel, cobalt, zinc, and copper, suggesting a possible biological role as broad-spectrum metallophores.
Assuntos
Produtos Biológicos , Micromonospora , Micromonospora/genética , Genômica , Metabolômica , Peptídeos/metabolismo , Família Multigênica , Produtos Biológicos/metabolismoRESUMO
Cyclic peptides have been excellent source of drug leads. With the advances in discovery platforms, the pharmaceutical industry has a growing interest in cyclic peptides and has pushed several into clinical trials. However, structural complexity of cyclic peptides brings extreme challenges for structure elucidation efforts. Isotopic fine structure analysis, Nuclear magnetic resonance (NMR), and detailed tandem mass spectrometry rapidly provided peptide sequence for streptnatamide A, a cyclic peptide isolated from a marine-derived Streptomyces sp. Marfey's analysis determined the stereochemistry of all amino acids, enabling the unambiguous structure determination of this compound. A non-ribosomal peptide synthetase biosynthetic gene cluster (stp) was tentatively identified and annotated for streptnatamide A based on the in silico analysis of whole genome sequencing data. These analytical tools will be powerful tools to overcome the challenges for cyclic peptide structure elucidation and accelerate the development of bioactive cyclic peptides.
Assuntos
Peptídeos Cíclicos , Streptomyces , Peptídeos Cíclicos/química , Streptomyces/metabolismo , Sequência de Aminoácidos , Aminoácidos/química , Espectrometria de Massas em Tandem/métodosRESUMO
Chemical investigations of a marine sponge-associated Bacillus revealed six new imidazolium-containing compounds, bacillimidazoles A-F (1-6). Previous reports of related imidazolium-containing natural products are rare. Initially unveiled by timsTOF (trapped ion mobility spectrometry) MS data, extensive HRMS and 1D and 2D NMR analyses enabled the structural elucidation of 1-6. In addition, a plausible biosynthetic pathway to bacillimidazoles is proposed based on isotopic labeling experiments and invokes the highly reactive glycolytic adduct 2,3-butanedione. Combined, the results of structure elucidation efforts, isotopic labeling studies and bioinformatics suggest that 1-6 result from a fascinating intersection of primary and secondary metabolic pathways in Bacillus sp. WMMC1349. Antimicrobial assays revealed that, of 1-6, only compound six displayed discernible antibacterial activity, despite the close structural similarities shared by all six natural products.
Assuntos
Antibacterianos/farmacologia , Bacillus , Poríferos , Animais , Antibacterianos/química , Organismos Aquáticos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade MicrobianaRESUMO
Lactobacillus crispatus is a well-established probiotic with antimicrobial activity against pathogens across several niches of the human body generally attributed to the production of bacteriostatic molecules, including hydrogen peroxide and lactic acid. Here, we show that the cell-free supernatants of clinical isolates of L. crispatus harbor robust bactericidal activity. We further identify phenyl-lactic acid as a bactericidal compound with properties and a susceptibility range nearly identical to that of the cell-free supernatant. As such, we hypothesize that phenyl-lactic acid is a key active ingredient in L. crispatus supernatant. IMPORTANCE Although Lactobacillus crispatus is an established commensal microbe frequently used in probiotics, its protective role in the bladder microbiome has not been clarified. We report here that some urinary isolates of L. crispatus exhibit bactericidal activity, primarily due to its ability to excrete phenyl-lactic acid into its environment. Both cell-free supernatants of L. crispatus isolates and phenyl-lactic acid exhibit bactericidal activity against a wide range of pathogens, including several that are resistant to multiple antibiotics.
Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Lactatos/metabolismo , Lactatos/farmacologia , Lactobacillus crispatus/metabolismo , Anti-Infecciosos/metabolismo , Bactérias/efeitos dos fármacos , Candida/efeitos dos fármacos , Lactatos/químicaRESUMO
Within animal-associated microbiomes, the functional roles of specific microbial taxa are often uncharacterized. Here, we use the fungus-growing ant system, a model for microbial symbiosis, to determine the potential defensive roles of key bacterial taxa present in the ants' fungus gardens. Fungus gardens serve as an external digestive system for the ants, with mutualistic fungi in the genus Leucoagaricus converting the plant substrate into energy for the ants. The fungus garden is host to specialized parasitic fungi in the genus Escovopsis. Here, we examine the potential role of Burkholderia spp. that occur within ant fungus gardens in inhibiting Escovopsis. We isolated members of the bacterial genera Burkholderia and Paraburkholderia from 50% of the 52 colonies sampled, indicating that members of the family Burkholderiaceae are common inhabitants in the fungus gardens of a diverse range of fungus-growing ant genera. Using antimicrobial inhibition bioassays, we found that 28 out of 32 isolates inhibited at least one Escovopsis strain with a zone of inhibition greater than 1 cm. Genomic assessment of fungus garden-associated Burkholderiaceae indicated that isolates with strong inhibition all belonged to the genus Burkholderia and contained biosynthetic gene clusters that encoded the production of two antifungals: burkholdine1213 and pyrrolnitrin. Organic extracts of cultured isolates confirmed that these compounds are responsible for antifungal activities that inhibit Escovopsis but, at equivalent concentrations, not Leucoagaricus spp. Overall, these new findings, combined with previous evidence, suggest that members of the fungus garden microbiome play an important role in maintaining the health and function of fungus-growing ant colonies. IMPORTANCE Many organisms partner with microbes to defend themselves against parasites and pathogens. Fungus-growing ants must protect Leucoagaricus spp., the fungal mutualist that provides sustenance for the ants, from a specialized fungal parasite, Escovopsis. The ants take multiple approaches, including weeding their fungus gardens to remove Escovopsis spores, as well as harboring Pseudonocardia spp., bacteria that produce antifungals that inhibit Escovopsis. In addition, a genus of bacteria commonly found in fungus gardens, Burkholderia, is known to produce secondary metabolites that inhibit Escovopsis spp. In this study, we isolated Burkholderia spp. from fungus-growing ants, assessed the isolates' ability to inhibit Escovopsis spp., and identified two compounds responsible for inhibition. Our findings suggest that Burkholderia spp. are often found in fungus gardens, adding another possible mechanism within the fungus-growing ant system to suppress the growth of the specialized parasite Escovopsis.
Assuntos
Antifúngicos/metabolismo , Formigas , Burkholderia/metabolismo , Hypocreales/crescimento & desenvolvimento , Lipopeptídeos/metabolismo , Parasitos/crescimento & desenvolvimento , Pirrolnitrina/metabolismo , Animais , Burkholderia/genética , Microbiota , Família Multigênica , Filogenia , SimbioseRESUMO
Three antifungal macrolides cyphomycin (1), caniferolide C (2) and GT-35 (3) were isolated from Streptomyces sp. ISID311, a bacterial symbiont associated with Cyphomyrmex fungus-growing ants. The planar structures of these compounds were established by 1 and 2D NMR data and MS analysis. The relative configurations of 1-3 were established using Kishi's universal NMR database method, NOE/ROE analysis and coupling constants analysis assisted by comparisons with NMR data of related compounds. Detailed bioinformatic analysis of cyphomycin biosynthetic gene cluster confirmed the stereochemical assignments. Compounds 1-3 displayed high antagonism against different strains of Escovopsis sp., pathogen fungi specialized to the fungus-growing ant system. Compounds 1-3 also exhibited potent antiprotozoal activity against intracellular amastigotes of the human parasite Leishmania donovani with IC50 values of 2.32, 0.091 and 0.073 µM, respectively, with high selectivity indexes.
Assuntos
Antiprotozoários/farmacologia , Leishmania donovani/efeitos dos fármacos , Macrolídeos/farmacologia , Streptomyces/química , Antiprotozoários/química , Antiprotozoários/isolamento & purificação , Relação Dose-Resposta a Droga , Macrolídeos/química , Macrolídeos/isolamento & purificação , Estrutura Molecular , Testes de Sensibilidade Parasitária , Relação Estrutura-AtividadeRESUMO
Chemical investigation of a marine sponge-associated Bacillus sp. led to the discovery of bacillibactins E and F (1 and 2). Despite containing the well-established cyclic triester core of iron-binding natural products such as enterobactin, bacillibactins E and F (1 and 2) are the first bacterial siderophores that contain nicotinic and benzoic acid moieties. The structures of the new compounds, including their absolute configurations, were determined by extensive spectroscopic analyses and Marfey's method. A plausible biosynthetic pathway to 1 and 2 is proposed; this route bears great similarity to other previously established bacillibactin-like pathways but appears to differentiate itself by a promiscuous DhbE, which likely installs the nicotinic moiety of 1 and the benzoic acid group of 2.
Assuntos
Bacillus/química , Enterobactina/química , Ferro/metabolismo , Poríferos/metabolismo , Sideróforos/química , Animais , Bacillus/metabolismo , Enterobactina/metabolismo , Ferro/química , Estrutura Molecular , Oligopeptídeos , Poríferos/químicaRESUMO
Antibiotic resistance and emerging viral pandemics have posed an urgent need for new anti-infective drugs. By screening our microbial extract library against the main protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the notorious ESKAPE pathogens, an active fraction was identified and purified, leading to an initial isolation of adipostatins A (1) and B (2). In order to diversify the chemical structures of adipostatins toward enhanced biological activities, a type III polyketide synthase was identified from the native producer, Streptomyces davawensis DSM101723, and was subsequently expressed in an E. coli host, resulting in the isolation of nine additional adipostatins 3-11, including two new analogs (9 and 11). The structures of 1-11 were established by HRMS, NMR, and chemical derivatization, including using a microgram-scale meta-chloroperoxybenzoic acid epoxidation-MS/MS analysis to unambiguously determine the double bond position in the alkyl chain. The present study discovered SARS-CoV-2 main protease inhibitory activity for the class of adipostatins for the first time. Several of the adipostatins isolated also exhibited antimicrobial activity against selected ESKAPE pathogens.
Assuntos
Aciltransferases/metabolismo , Anti-Infecciosos/química , Proteínas de Bactérias/metabolismo , Resorcinóis/química , Aciltransferases/antagonistas & inibidores , Aciltransferases/classificação , Aciltransferases/genética , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/metabolismo , Anti-Infecciosos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/classificação , Proteínas de Bactérias/genética , COVID-19/patologia , COVID-19/virologia , Proteases 3C de Coronavírus/antagonistas & inibidores , Proteases 3C de Coronavírus/metabolismo , Avaliação Pré-Clínica de Medicamentos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Conformação Molecular , Filogenia , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Resorcinóis/isolamento & purificação , Resorcinóis/metabolismo , Resorcinóis/farmacologia , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/metabolismo , Streptomyces/enzimologia , Espectrometria de Massas em TandemRESUMO
Chemistry drives many biological interactions between the microbiota and host animals, yet it is often challenging to identify the chemicals involved. This poses a problem, as such small molecules are excellent sources of potential pharmaceuticals, pretested by nature for animal compatibility. We discovered anti-HIV compounds from small, marine tunicates from the Eastern Fields of Papua New Guinea. Tunicates are a reservoir for new bioactive chemicals, yet their small size often impedes identification or even detection of the chemicals within. We solved this problem by combining chemistry, metagenomics, and synthetic biology to directly identify and synthesize the natural products. We show that these anti-HIV compounds, the divamides, are a novel family of lanthipeptides produced by symbiotic bacteria living in the tunicate. Neighboring animal colonies contain structurally related divamides that differ starkly in their biological properties, suggesting a role for biosynthetic plasticity in a native context wherein biological interactions take place.
Assuntos
Fármacos Anti-HIV/farmacologia , Produtos Biológicos/farmacologia , Descoberta de Drogas , Infecções por HIV/tratamento farmacológico , Microbiota , Simbiose , Animais , Bactérias , DNA/análise , Avaliação Pré-Clínica de Medicamentos , Genômica , Humanos , Lisinoalanina/química , Metagenoma , Metagenômica , Família Multigênica , Peptídeos/farmacologia , Relação Estrutura-Atividade , Biologia Sintética , Linfócitos T/efeitos dos fármacos , UrocordadosRESUMO
Keywords: NDM-1 inhibitors; marine-derived Streptomyces sp.; carbapenem-resistant Enterobacteriaceae; metal chelators.
Assuntos
Antibacterianos/síntese química , Complexos de Coordenação/síntese química , Complexos de Coordenação/farmacologia , Piridinas/síntese química , Piridinas/farmacologia , Inibidores de beta-Lactamases/síntese química , beta-Lactamases/metabolismo , Antibacterianos/química , Antibacterianos/farmacologia , Complexos de Coordenação/química , Meropeném/farmacologia , Testes de Sensibilidade Microbiana , Piridinas/isolamento & purificação , Inibidores de beta-Lactamases/farmacologia , beta-Lactamases/químicaRESUMO
Bacterial symbionts frequently provide chemical defenses for their hosts, and such systems can provide discovery pathways to new antifungals and structurally intriguing metabolites. This report describes a small family of naturally occurring small molecules with chimeric structures and a mixed biosynthesis that features an unexpected but key nonenzymatic step. An insect-associated Pseudomonas protegens strain's activity in an in vivo murine candidiasis assay led to the discovery of a family of highly hydrogen-deficient metabolites. Bioactivity- and mass-guided fractionation led to the pyonitrins, highly complex aromatic metabolites in which 10 of the 20 carbons are quaternary, and 7 of them are contiguous. The P. protegens genome revealed that the production of the pyonitrins is the result of a spontaneous reaction between biosynthetic intermediates of two well-studied Pseudomonas metabolites, pyochelin and pyrrolnitrin. The combined discovery of the pyonitrins and identification of the responsible biosynthetic gene clusters revealed an unexpected biosynthetic route that would have prevented the discovery of these metabolites by bioinformatic analysis alone.
Assuntos
Produtos Biológicos/química , Produtos Biológicos/metabolismo , Pseudomonas/metabolismo , Animais , Antifúngicos/química , Antifúngicos/metabolismo , Antifúngicos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Produtos Biológicos/farmacologia , Vias Biossintéticas/genética , Candida albicans/efeitos dos fármacos , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Cromatografia Líquida de Alta Pressão , Avaliação Pré-Clínica de Medicamentos/métodos , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Fenóis/metabolismo , Pseudomonas/genética , Pirrolnitrina/biossíntese , Tiazóis/metabolismoRESUMO
Here we report the discovery of two new 3-acetamido-4-hydroxybenzoate esters, bulbiferates A (1) and B (2), isolated from Microbulbifer sp. cultivated from the marine tunicate Ecteinascidia turbinata. The structures of 1 and 2 were determined by analysis of 2D NMR and MS data. Additionally, three synthetic analogues (3-5), differing in ester sizes/lengths, were prepared for the purposes of evaluating potential structure-activity relationships; no clear correlations tying ester lengths to activity were evident. Bulbiferates A (1) and B (2) demonstrated antibacterial activity against both Escherichia coli (E. coli) and methicillin-sensitive Staphylococcus aureus (MSSA), whereas the synthetic analogues 3 and 4 displayed activity only against MSSA.
Assuntos
Antibacterianos/farmacologia , Gammaproteobacteria/química , Água do Mar/microbiologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Análise Espectral/métodos , Relação Estrutura-AtividadeRESUMO
Integrating MS-based metabolomics approaches, LC-MS-PCA and molecular networking enabled the targeted isolation of five new pyrrole-derived alkaloids, phallusialides A-E (1-5), from a marine-derived Micromonospora sp. bacterium. The structures of 1-5 were elucidated by analysis of their HRMS, MS/MS, and NMR spectroscopic data. The absolute configuration of phallusialide A (1) was determined on the basis of comparisons of experimental and theoretically calculated ECD spectra. Compounds 1 and 2 exhibited antibacterial activity against methicillin resistant S. aureus (MRSA) and E. coli, with MIC values of 32 and 64 µg/mL, respectively, whereas 3-5 showed no antibacterial activity even at 256 µg/mL, yielding important SAR insights for this class of compounds.
Assuntos
Alcaloides/isolamento & purificação , Metabolômica , Micromonospora/metabolismo , Pirróis/química , Análise Espectral/métodos , Alcaloides/química , Alcaloides/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura MolecularRESUMO
To date, studies describing myxobacterial secondary metabolites have been relatively scarce in comparison to those addressing actinobacterial secondary metabolites. This realization suggests the immense potential of myxobacteria as an intriguing source of secondary metabolites with unusual structural features and a wide array of biological activities. Marine-derived myxobacteria are especially attractive due to their unique biosynthetic gene clusters, although they are more difficult to handle than terrestrial myxobacteria. Here, we report the discovery of two new pyrazinone-type molecules, enhypyrazinones A and B, from a marine-derived myxobacterium Enhygromyxa sp. Their structures were elucidated by HRESIMS and comprehensive NMR data analyses. Compounds 1 and 2, which contain a rare trisubstituted-pyrazinone core, represent a unique class of molecules from Enhygromyxa sp.
Assuntos
Produtos Biológicos/isolamento & purificação , Indóis/isolamento & purificação , Myxococcales/metabolismo , Pirazinas/isolamento & purificação , Produtos Biológicos/química , Indóis/química , Imageamento por Ressonância Magnética , Pirazinas/química , Metabolismo SecundárioRESUMO
Covering: 2010 up to 2017Life on Earth is characterized by a remarkable abundance of symbiotic and highly refined relationships among life forms. Defined as any kind of close, long-term association between two organisms, symbioses can be mutualistic, commensalistic or parasitic. Historically speaking, selective pressures have shaped symbioses in which one organism (typically a bacterium or fungus) generates bioactive small molecules that impact the host (and possibly other symbionts); the symbiosis is driven fundamentally by the genetic machineries available to the small molecule producer. The human microbiome is now integral to the most recent chapter in animal-microbe symbiosis studies and plant-microbe symbioses have significantly advanced our understanding of natural products biosynthesis; this also is the case for studies of fungal-microbe symbioses. However, much less is known about microbe-microbe systems involving interspecies interactions. Microbe-derived small molecules (i.e. antibiotics and quorum sensing molecules, etc.) have been shown to regulate transcription in microbes within the same environmental niche, suggesting interspecies interactions whereas, intraspecies interactions, such as those that exploit autoinducing small molecules, also modulate gene expression based on environmental cues. We, and others, contend that symbioses provide almost unlimited opportunities for the discovery of new bioactive compounds whose activities and applications have been evolutionarily optimized. Particularly intriguing is the possibility that environmental effectors can guide laboratory expression of secondary metabolites from "orphan", or silent, biosynthetic gene clusters (BGCs). Notably, many of the studies summarized here result from advances in "omics" technologies and highlight how symbioses have given rise to new anti-bacterial and antifungal natural products now being discovered.
Assuntos
Antibacterianos , Simbiose/fisiologia , Animais , Bactérias/metabolismo , Evolução Biológica , Fungos/fisiologia , Humanos , Estrutura Molecular , Família Multigênica , Plantas/metabolismoRESUMO
Here we describe the rapid identification and prioritization of novel active marine natural products using an improved dereplication strategy. During the course of our screening of marine natural product libraries, a new cyclic trihydroxamate compound, thalassosamide, was discovered from the α-proteobacterium Thalassospira profundimaris. Its structure was determined by 2D NMR and MS/MS experiments, and the absolute configuration of the lysine-derived units was established by Marfey's analysis, whereas that of C-9, 9', and 9â³ was determined via the circular dichroism data of the [Rh2(OCOCF3)4] complex and DFT NMR calculations. Thalassosamide showed moderate in vivo efficacy against Pseudomonas aeruginosa.
Assuntos
Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Ácidos Hidroxâmicos/isolamento & purificação , Pseudomonas aeruginosa/química , Sideróforos/química , Sideróforos/isolamento & purificação , Sideróforos/farmacologia , Produtos Biológicos/química , Dicroísmo Circular , Ácidos Hidroxâmicos/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Espectrometria de Massas em TandemRESUMO
Despite the fact that actinomycetes harbor the genetic potential to produce terpenes, terpenoid natural products tend to be a rare occurrence in fermentation broths. Here we report two new halimane-type diterpenoids, micromonohalimanes A (1) and B (2), that were isolated from a Micromonospora sp. cultivated from the marine ascidian Symplegma brakenhielmi. This is the first report of the halimane-type diterpenoids from Micromonospora. The structures were determined using spectroscopic methods including X-ray crystallography to establish the absolute configuration. Micromonohalimane B demonstrated moderate antibacterial activity against methicillin-resistant Staphylococcus aureus.
Assuntos
Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Micromonospora/química , Animais , Antibacterianos/química , Cristalografia por Raios X , Diterpenos/química , Florida , Biologia Marinha , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Urocordados/microbiologiaRESUMO
Despite the advances in NMR, structure determination is often slow and constitutes a bottleneck in natural products discovery. Removal of this bottleneck would greatly improve the throughput for antibiotic discovery as well as other therapeutic areas. Overall, faster structure methods for structure determination will serve the natural products community in a broad manner. This report describes the first application of 3D NMR for elucidation of two microbially produced peptide natural products with novel structures. The methods are cost-effective and greatly improve the confidence in a proposed structure.