Nomimicins B-D, new tetronate-class polyketides from a marine-derived actinomycete of the genus Actinomadura.
Ontology highlight
ABSTRACT:
SUBMITTER: Zhang Z
PROVIDER: S-EPMC8404215 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Aside from the well-studied conventional actinomycetes such as Streptomyces, the less investigated genera of actinomycetes also represent a promising source of natural products. Genome mining indicated that members of the underexplored genus Pseudosporangium, from which no secondary metabolites have been reported to date, may harbor the biosynthetic machinery for the formation of novel natural products. The strain RD062863, that is available at a public culture collection, was obtained and subjected to metabolite analysis, which resulted in the discovery of a novel cyclopeptide, pseudosporamide (1), along with three new oligomycin-class polyketides, pseudosporamicins A-C (2-4). The unusual structure of compound 1, featured by a biaryl-bond bridging across a tripeptide scaffold, N-acetyl-ʟ-Tyr-ʟ-Pro-ʟ-Trp, was determined by a combination of spectroscopic analyses, chemical derivatization, ECD calculation, and DFT-based theoretical chemical shift calculation, revealing the presence of an (S a)-axial chirality around the biaryl bond. Compounds 2-4 lacked hydroxylation on the side chain of the spiroacetal rings, which showed clear contrast to other oligomycin congeners and related polyketides with ring-truncation or expansion. The new macrolides 2-4 displayed potent antimicrobial activity against the Gram-positive bacterium Kocuria rhizohpila and the plant pathogenic fungus Glomerella cingulata. All compounds showed moderate cytotoxicity against P388 murine leukemia cells with IC50 values in the micromolar to submicromolar ranges. These results exemplified the validity of phylogeny-focused strain selection combined with biosynthetic gene-directed genome mining for the efficient discovery of new natural products.
| S-EPMC7277628 | biostudies-literature
Project description:Chemical examination of a phylogenetically unique strain of the obligate marine actinomycete Salinispora pacifica led to the discovery of four new polyketides, salinipyrones A and B ( 1, 2) and pacificanones A and B ( 3, 4). These compounds appear to be derived from a mixed-precursor polyketide biosynthesis involving acetate, propionate, and butyrate building blocks. Spectral analysis, employing NMR, IR, UV, and CD methods and chemical derivatization, was used to assign the structures and absolute configurations of these new metabolites. Salinipyrones A and B displayed exactly opposite CD spectra, indicating their pseudoenantiomeric relationship. This relationship was shown to be a consequence of the geometric isomerization of one double bond. The phenomenon of polyketide module skipping is proposed to explain the unusual biosynthesis of the salinipyrones and the pacificanones.
| S-EPMC2820078 | biostudies-literature
Project description:Two new polyene macrolides, marinisporolides A and B (1, 2), were isolated from the saline culture of the marine actinomycete, strain CNQ-140, identified as a member of the new marine genus Marinispora. The marinisporolides are 34-membered macrolides composed of a conjugated pentaene and several pairs of 1,3-dihydroxyl functionalities. Marinisporolide A (1) contains a bicyclic spiro-bis-tetrahydropyran ketal functionality, while marinisporolide B (2) is the corresponding hemiketal. The structures of these new compounds were assigned by combined spectral and chemical methods including extensive 2D NMR experiments and correlations of (13)C NMR data with Kishi's Universal NMR Database. Chemical modifications, including methanolysis, acetonide formation, and application of the modified Mosher method, provided the full stereostructures of these molecules. Three additional macrolides, marinisporolides C-E (3-5), which are olefin geometric isomers of marinisporolide A (1), were also isolated and their structures defined. Under room light, marinisporolides A and B readily photoisomerize to C-E indicating that they are most likely produced by photochemical conversion during the cultivation or isolation procedures. Although polyenes, marinisporolides A (1) and B (2) showed weak to no antifungal activity against Candida albicans.
| S-EPMC3186066 | biostudies-literature
Project description:Marine-derived fungi have been reported to have great potential to produce structurally unique metabolites. Our investigation on secondary metabolites from marine-derived fungi resulted in the isolation of seven new polyketides (phomopsiketones D-G (1-4) and letendronols A-C (5-7)) as well as one known xylarinol (8) in the cultural broth of Letendraea sp. Their structures and absolute configurations were elucidated using a set of spectroscopic and chemical methods, including HRESIMS, NMR, single-crystal X-ray diffraction, ECD calculation, and a modified version of Mosher's method. Compound 2 showed weak inhibition against nitric oxide production in lipopolysaccaride-activated macrophages with an IC50 value of 86 μM.
| S-EPMC7024145 | biostudies-literature
Project description:BackgroundThere is little published regarding metabolism of Salinispora species. In continuation with efforts performed towards this goal, this study is focused on new insights into the metabolism of the three-identified species of Salinispora using constraints-based modeling. At present, only one manually curated genome-scale metabolic model (GSM) for Salinispora tropica strain CNB-440T has been built despite the role of Salinispora strains in drug discovery.ResultsHere, we updated, and expanded the scope of the model of Salinispora tropica CNB-440T, and GSMs were constructed for two sequenced type strains covering the three-identified species. We also constructed a Salinispora core model that contains the genes shared by 93 sequenced strains and a few non-conserved genes associated with essential reactions. The models predicted no auxotrophies for essential amino acids, which was corroborated experimentally using a defined minimal medium (DMM). Experimental observations suggest possible sulfur accumulation. The Core metabolic content shows that the biosynthesis of specialised metabolites is the less conserved subsystem. Sets of reactions were analyzed to explore the differences between the reconstructions. Unique reactions associated to each GSM were mainly due to genome sequence data except for the ST-CNB440 reconstruction. In this case, additional reactions were added from experimental evidence. This reveals that by reaction content the ST-CNB440 model is different from the other species models. The differences identified in reaction content between models gave rise to different functional predictions of essential nutrient usage by each species in DMM. Furthermore, models were used to evaluate in silico single gene knockouts under DMM and complex medium. Cluster analysis of these results shows that ST-CNB440, and SP-CNR114 models are more similar when considering predicted essential genes.ConclusionsModels were built for each of the three currently identified Salinispora species, and a core model representing the conserved metabolic capabilities of Salinispora was constructed. Models will allow in silico metabolism studies of Salinispora strains, and help researchers to guide and increase the production of specialised metabolites. Also, models can be used as templates to build GSMs models of closely related organisms with high biotechnology potential.
| S-EPMC6341766 | biostudies-literature
Project description:Actinomycetes are remarkable producers of compounds essential for human and veterinary medicine as well as for agriculture. The genomes of those microorganisms possess several sets of genes (biosynthetic gene cluster (BGC)) encoding pathways for the production of the valuable secondary metabolites. A significant proportion of the identified BGCs in actinomycetes encode pathways for the biosynthesis of polyketide compounds, nonribosomal peptides, or hybrid products resulting from the combination of both polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs). The potency of these molecules, in terms of bioactivity, was recognized in the 1940s, and started the "Golden Age" of antimicrobial drug discovery. Since then, several valuable polyketide drugs, such as erythromycin A, tylosin, monensin A, rifamycin, tetracyclines, amphotericin B, and many others were isolated from actinomycetes. This review covers the most relevant actinomycetes-derived polyketide drugs with antimicrobial activity, including anti-fungal agents. We provide an overview of the source of the compounds, structure of the molecules, the biosynthetic principle, bioactivity and mechanisms of action, and the current stage of development. This review emphasizes the importance of actinomycetes-derived antimicrobial polyketides and should serve as a "lexicon", not only to scientists from the Natural Products field, but also to clinicians and others interested in this topic.
| S-EPMC6963833 | biostudies-literature
Project description:The sponge-derived fungus Penicillium sp. SCSIO41015 cultured on solid rice medium yielded twenty-one compounds (1-21), including two new alkaloids (1 and 2) and one new pyrone derivative (3). Their structures were elucidated by analysis of 1D/2D NMR data and HR-ESI-MS. Their absolute configurations were established by single-crystal X-ray diffraction analysis and comparison of the experimental with reported specific rotation values. Compound 16 exhibited selective cytotoxic activity against the human gastric cancer cells MGC803, with IC50 value of 5.19 μM. Compounds 9 and 18 showed weak antibacterial activity against Staphylococcus aureus and Acinetobacter baumannii, respectively, both with MIC values of 57 μg/mL. Furthermore, compound 16 displayed potent antibacterial activity against S. aureus with an MIC value of 3.75 μg/mL.
| S-EPMC6669684 | biostudies-literature
Project description:Eighteen polyketides (1-18) including six citrinin derivatives, two phenol derivatives, one cyclopentenone, two naphthol derivatives, and seven tetralone derivatives were isolated from the culture broth of a marine-derived fungal strain Xylariaceae sp. SCSGAF0086. Five of these compounds (1, 2, 8, 9, and 10) were new, and their structures were determined by spectroscopic methods. Compounds 4, 6, 7, and 17 showed enzyme-inhibitory activities towards several tested enzymes, and 6 and 7 showed strong antifouling activity against Bugula neritina larvae settlement. This is the first time that the antifouling and enzyme-inhibitory activities of these compounds has been reported.
| S-EPMC3707170 | biostudies-literature
Project description:This review covers the initial discovery of the marine actinomycete genus Salinispora through its development as a model for natural product research. A focus is placed on the novel chemical structures reported with reference to their biological activities and the synthetic and biosynthetic studies they have inspired. The time line of discoveries progresses from more traditional bioassay-guided approaches through the application of genome mining and genetic engineering techniques that target the products of specific biosynthetic gene clusters. This overview exemplifies the extraordinary biosynthetic diversity that can emanate from a narrowly defined genus and supports future efforts to explore marine taxa in the search for novel natural products.
| S-EPMC4414829 | biostudies-literature
Project description:Access to genome sequence data has challenged traditional natural product discovery paradigms by revealing that the products of most bacterial biosynthetic pathways have yet to be discovered. Despite the insight afforded by this technology, little is known about the diversity and distributions of natural product biosynthetic pathways among bacteria and how they evolve to generate structural diversity. Here we analyze genome sequence data derived from 75 strains of the marine actinomycete genus Salinispora for pathways associated with polyketide and nonribosomal peptide biosynthesis, the products of which account for some of today's most important medicines. The results reveal high levels of diversity, with a total of 124 pathways identified and 229 predicted with continued sequencing. Recent horizontal gene transfer accounts for the majority of pathways, which occur in only one or two strains. Acquired pathways are incorporated into genomic islands and are commonly exchanged within and between species. Acquisition and transfer events largely involve complete pathways, which subsequently evolve by gene gain, loss, and duplication followed by divergence. The exchange of similar pathway types at the precise chromosomal locations in different strains suggests that the mechanisms of integration include pathway-level homologous recombination. Despite extensive horizontal gene transfer there is clear evidence of species-level vertical inheritance, supporting the concept that secondary metabolites represent functional traits that help define Salinispora species. The plasticity of the Salinispora secondary metabolome provides an effective mechanism to maximize population-level secondary metabolite diversity while limiting the number of pathways maintained within any individual genome.
| S-EPMC3970525 | biostudies-literature