Wei Bin, Du Ao-Qi, Zhou Zhen-Yi, Lai Cong, Yu Wen-Chao, Yu Jin-Biao, Yu Yan-Lei, Chen Jian-Wei, Zhang Hua-Wei, Xu Xue-Wei, Wang Hong
College of Pharmaceutical Science & Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, 310014, China.
Key Laboratory of Marine Ecosystem and Biogeochemistry, State Oceanic Administration & Second Institute of Oceanography, Ministry of Natural Resources, Hangzhou, 310012, China.
Environ Microbiol. 2021 Nov;23(11):6981-6992. doi: 10.1111/1462-2920.15761. Epub 2021 Sep 21.
Bacterial secondary metabolites are rich sources of novel drug leads. The diversity of secondary metabolite biosynthetic gene clusters (BGCs) in genome-sequenced bacteria, which will provide crucial information for the efficient discovery of novel natural products, has not been systematically investigated. Here, the distribution and genetic diversity of BGCs in 10 121 prokaryotic genomes (across 68 phyla) were obtained from their PRISM4 outputs using a custom python script. A total of 18 043 BGCs are detected from 5743 genomes with non-ribosomal peptide synthetases (25.4%) and polyketides (15.9%) as the dominant classes of BGCs. Bacterial strains harbouring the largest number of BGCs are revealed and BGC count in strains of some genera vary greatly, suggesting the necessity of individually evaluating the secondary metabolism potential. Additional analysis against 102 strains of discovered bacterial genera with abundant amounts of BGCs confirms that Kutzneria, Kibdelosporangium, Moorea, Saccharothrix, Cystobacter, Archangium, Actinosynnema, Kitasatospora, and Nocardia, may also be important sources of natural products and worthy of priority investigation. Comparative analysis of BGCs within these genera indicates the great diversity and novelty of the BGCs. This study presents an atlas of bacterial secondary metabolite BGCs that provides a lot of key information for the targeted discovery of novel natural products.
细菌次级代谢产物是新型药物先导物的丰富来源。基因组测序细菌中次级代谢产物生物合成基因簇（BGCs）的多样性尚未得到系统研究，而这将为高效发现新型天然产物提供关键信息。在这里，使用自定义Python脚本从PRISM4输出中获得了10121个原核生物基因组（跨越68个门）中BGCs的分布和遗传多样性。从5743个基因组中总共检测到18043个BGCs，其中非核糖体肽合成酶（25.4%）和聚酮化合物（15.9%）是BGCs的主要类别。揭示了拥有BGCs数量最多的细菌菌株，并且某些属的菌株中BGCs数量差异很大，这表明有必要单独评估次级代谢潜力。对102株发现的含有大量BGCs的细菌属进行的额外分析证实，库茨涅尔菌属、纤维堆囊菌属、莫雷阿属、糖丝菌属、孢囊杆菌属、原囊菌属、放线共生菌属、北里孢菌属和诺卡氏菌属也可能是天然产物的重要来源，值得优先研究。这些属内BGCs的比较分析表明了BGCs的巨大多样性和新颖性。本研究展示了一份细菌次级代谢产物BGCs图谱，为靶向发现新型天然产物提供了许多关键信息。
