Phylogenomic analysis uncovers an unexpected capacity for the biosynthesis of secondary metabolites in Pseudoalteromonas

IF 6 2区 医学 Q1 CHEMISTRY, MEDICINAL
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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 (14), 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.

Abstract Image

系统发生组分析发现假交替单胞菌具有意想不到的次生代谢物生物合成能力。
假交替单胞菌(Pseudoalteromonas)是一种海洋细菌属,也是具有抗菌、抗真菌和防污生物活性的天然产品的良好来源。为了加速探索该属的新化合物,我们采用基因优先方法研究了 632 个公开的假交替单胞菌基因组。我们发现了 3968 个参与次生代谢物生物合成的生物合成基因簇(BGCs),并将其分为 995 个基因簇家族(GCFs)。令人惊讶的是,只有 9 个 GCFs(0.9%)包含了从生物合成基因簇最低信息数据库(MIBiG)中实验鉴定的参考生物合成基因簇,这表明假交替单胞菌中的次生代谢物具有惊人的新颖性。通过对已鉴定的 BGCs 所编码的生物合成多样性进行生物信息学分析,发现该属的六个优势种(P. citrea、P. flavipulchra、P. luteoviolacea、P. maricaloris、P. piscicida 和 P. rubra)平均编码超过 17 个 BGCs。此外,每个物种的 BGC 分布都具有物种特异性。不过,深入分析发现,在六个优势物种中,有两个 BGC 在五个物种中保持一致。这些BGCs编码了一种未知的lanthipeptide和嗜苷酸性物质myxochelin B,这意味着抗生素对假交替单胞菌起着至关重要的作用。我们对来自 6 个优势种的 11 株菌株进行了化学分析,并从 P. citrea WJX-3 中鉴定出了 4 种新抗生素--科罗米星 L-O(1-4)。我们的研究结果凸显了假交替单胞菌中生物活性化合物尚未开发的生物合成潜力,并为目标探索提供了重要指导。
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来源期刊
CiteScore
11.70
自引率
9.00%
发文量
863
审稿时长
29 days
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.
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