Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, Health Science Center, Ningbo University, Ningbo, Zhejiang, 315211, China.
College of Food Science and Engineering, Ningbo University, Ningbo, Zhejiang, 315832, China.
Eur J Med Chem. 2024 Dec 5;279:116840. doi: 10.1016/j.ejmech.2024.116840. Epub 2024 Sep 5.
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.
假交替单胞菌是海洋细菌的一个属，是具有抗菌、抗真菌和抗污生物活性的天然产物的有前途的来源。为了加速从该属中探索新化合物，我们采用基因优先方法研究了 632 个公共假交替单胞菌基因组。我们确定了 3968 个涉及次生代谢物生物合成的生物合成基因簇（BGC），并将其分类为 995 个基因簇家族（GCF）。令人惊讶的是，只有 9 个 GCF（0.9%）包含来自最小信息关于生物合成基因簇数据库（MIBiG）的实验鉴定的参考生物合成基因簇，这表明假交替单胞菌中次生代谢物具有惊人的新颖性。对鉴定的 BGC 中编码的生物合成多样性的生物信息学分析揭示了该属的六种主要物种，即 P. citrea、P. flavipulchra、P. luteoviolacea、P. maricaloris、P. piscicida 和 P. rubra，它们平均编码超过 17 个 BGC。此外，每种物种都表现出 BGC 的种特异性分布。然而，深入分析显示，有两个 BGC 在六种主要物种中的五种中保守。这些 BGC 编码一种未知的类硫肽和铁载体 myxochelin B，这意味着抗生素对假交替单胞菌具有重要作用。我们从六种主要物种的 11 株菌株中进行了化学分析，并从 P. citrea WJX-3 中鉴定出四种新抗生素，即 korormicins L-O（1-4）。我们的结果突出了假交替单胞菌中生物活性化合物的未开发生物合成潜力，并为靶向探索提供了重要指导。
