Global analysis of the biosynthetic chemical space of marine prokaryotes

Microbiome

Research

Cai-Ling Yang¹  Hong Wang¹  Zhen-Yi Zhou¹  Ao-Qi Du¹  Wen-Chao Yu¹  Yan-Lei Yu¹  Jian-Wei Chen¹  Hua-Wei Zhang¹  Gang-Ao Hu¹  Bin Wei²  Qihao Wu³  Qi Xuan⁴  Xue-Wei Xu⁵ 

[1] College of Pharmaceutical Science & Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Key Laboratory of Marine Fishery Resources Exploitment & Utilization of Zhejiang Province, Zhejiang University of Technology, 310014, Hangzhou, China;College of Pharmaceutical Science & Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Key Laboratory of Marine Fishery Resources Exploitment & Utilization of Zhejiang Province, Zhejiang University of Technology, 310014, Hangzhou, China;Key Laboratory of Marine Ecosystem and Biogeochemistry, Ministry of Natural Resources & Second Institute of Oceanography, Ministry of Natural Resources, 310012, Hangzhou, China;Department of Chemistry, Institute of Biomolecular Design & Discovery, Yale University, 06516, West Haven, CT, USA;Institute of Cyberspace Security, College of Information Engineering, Zhejiang University of Technology, 310023, Hangzhou, China;Key Laboratory of Marine Ecosystem and Biogeochemistry, Ministry of Natural Resources & Second Institute of Oceanography, Ministry of Natural Resources, 310012, Hangzhou, China;

关键词: Marine prokaryotes;    Biosynthetic gene clusters;    Secondary metabolite;    Genomics;    Cheminformatics;   

DOI  :  10.1186/s40168-023-01573-3

 received in 2023-01-13, accepted in 2023-05-15,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundMarine prokaryotes are a rich source of novel bioactive secondary metabolites for drug discovery. Recent genome mining studies have revealed their great potential to bio-synthesize novel secondary metabolites. However, the exact biosynthetic chemical space encoded by the marine prokaryotes has yet to be systematically evaluated.ResultsWe first investigated the secondary metabolic potential of marine prokaryotes by analyzing the diversity and novelty of the biosynthetic gene clusters (BGCs) in 7541 prokaryotic genomes from cultivated and single cells, along with 26,363 newly assembled medium-to-high-quality genomes from marine environmental samples. To quantitatively evaluate the unexplored biosynthetic chemical space of marine prokaryotes, the clustering thresholds for constructing the biosynthetic gene cluster and molecular networks were optimized to reach a similar level of the chemical similarity between the gene cluster family (GCF)-encoded metabolites and molecular family (MF) scaffolds using the MIBiG database. The global genome mining analysis demonstrated that the predicted 70,011 BGCs were organized into 24,536 mostly new (99.5%) GCFs, while the reported marine prokaryotic natural products were only classified into 778 MFs at the optimized clustering thresholds. The number of MF scaffolds is only 3.2% of the number of GCF-encoded scaffolds, suggesting that at least 96.8% of the secondary metabolic potential in marine prokaryotes is untapped. The unexplored biosynthetic chemical space of marine prokaryotes was illustrated by the 88 potential novel antimicrobial peptides encoded by ribosomally synthesized and post-translationally modified peptide BGCs. Furthermore, a sea-water-derived Aquimarina strain was selected to illustrate the diverse biosynthetic chemical space through untargeted metabolomics and genomics approaches, which identified the potential biosynthetic pathways of a group of novel polyketides and two known compounds (didemnilactone B and macrolactin A 15-ketone).ConclusionsThe present bioinformatics and cheminformatics analyses highlight the promising potential to explore the biosynthetic chemical diversity of marine prokaryotes and provide valuable knowledge for the targeted discovery and biosynthesis of novel marine prokaryotic natural products.8qkWfGqcrPbn_o7-XLBWPjVideo Abstract

【 授权许可】

CC BY   
© The Author(s) 2023

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