{"title":"Phylogenomic analysis uncovers an unexpected capacity for the biosynthesis of secondary metabolites in Pseudoalteromonas","authors":"","doi":"10.1016/j.ejmech.2024.116840","DOIUrl":null,"url":null,"abstract":"<div><p><em>Pseudoalteromonas</em> is a genus of marine bacteria and a promising source of natural products with antibacterial, antifungal, and antifouling bioactivities<em>.</em> To accelerate the exploration of new compounds from this genus, we applied the gene-first approach to study 632 public <em>Pseudoalteromonas</em> genomes. We identified 3968 biosynthetic gene clusters (BGCs) involved in the biosynthesis of secondary metabolites and classified them into 995 gene cluster families (GCFs). Surprisingly, only 9 GCFs (0.9 %) included an experimentally identified reference biosynthetic gene cluster from the Minimum Information about a Biosynthetic Gene cluster database (MIBiG), suggesting a striking novelty of secondary metabolites in <em>Pseudoalteromonas</em>. Bioinformatic analysis of the biosynthetic diversity encoded in the identified BGCs uncovered six dominant species of this genus, <em>P. citrea</em>, <em>P. flavipulchra</em>, <em>P. luteoviolacea</em>, <em>P. maricaloris</em>, <em>P. piscicida</em>, and <em>P. rubra</em>, that encoded more than 17 BGCs on average. Moreover, each species exhibited a species-specific distribution of BGC. However, a deep analysis revealed two BGCs conserved across five of the six dominant species. These BGCS encoded an unknown lanthipeptide and the siderophore myxochelin B implying an essential role of antibiotics for <em>Pseudoalteromonas.</em> We chemically profiled 11 strains from the 6 dominant species and identified four new antibiotics, korormicins L-O (<strong>1</strong>–<strong>4</strong>), from <em>P. citrea</em> WJX-3. Our results highlight the unexplored biosynthetic potential for bioactive compounds in <em>Pseudoalteromonas</em> and provide an important guideline for targeting exploration.</p></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":6.0000,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0223523424007219","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Pseudoalteromonas is a genus of marine bacteria and a promising source of natural products with antibacterial, antifungal, and antifouling bioactivities. To accelerate the exploration of new compounds from this genus, we applied the gene-first approach to study 632 public Pseudoalteromonas genomes. We identified 3968 biosynthetic gene clusters (BGCs) involved in the biosynthesis of secondary metabolites and classified them into 995 gene cluster families (GCFs). Surprisingly, only 9 GCFs (0.9 %) included an experimentally identified reference biosynthetic gene cluster from the Minimum Information about a Biosynthetic Gene cluster database (MIBiG), suggesting a striking novelty of secondary metabolites in Pseudoalteromonas. Bioinformatic analysis of the biosynthetic diversity encoded in the identified BGCs uncovered six dominant species of this genus, P. citrea, P. flavipulchra, P. luteoviolacea, P. maricaloris, P. piscicida, and P. rubra, that encoded more than 17 BGCs on average. Moreover, each species exhibited a species-specific distribution of BGC. However, a deep analysis revealed two BGCs conserved across five of the six dominant species. These BGCS encoded an unknown lanthipeptide and the siderophore myxochelin B implying an essential role of antibiotics for Pseudoalteromonas. We chemically profiled 11 strains from the 6 dominant species and identified four new antibiotics, korormicins L-O (1–4), from P. citrea WJX-3. Our results highlight the unexplored biosynthetic potential for bioactive compounds in Pseudoalteromonas and provide an important guideline for targeting exploration.
期刊介绍:
The European Journal of Medicinal Chemistry is a global journal that publishes studies on all aspects of medicinal chemistry. It provides a medium for publication of original papers and also welcomes critical review papers.
A typical paper would report on the organic synthesis, characterization and pharmacological evaluation of compounds. Other topics of interest are drug design, QSAR, molecular modeling, drug-receptor interactions, molecular aspects of drug metabolism, prodrug synthesis and drug targeting. The journal expects manuscripts to present the rational for a study, provide insight into the design of compounds or understanding of mechanism, or clarify the targets.