Nitric oxide synthase-guided genome mining identifies a cytochrome P450 enzyme for olefin nitration in bacterial specialized metabolism  

作　　者：Hu Li Wei Li Kaihui Song Yu Liu Guiyun Zhao Yi-Ling Du 

机构地区：[1]Polytechnic Institute,Zhejiang University,Hangzhou,310022,China [2]Department of Microbiology,Zhejiang University School of Medicine,Hangzhou,310058,China [3]College of Life Sciences,Zhejiang University,310058,Hangzhou,China

出　　处：《Synthetic and Systems Biotechnology》2024年第1期127-133,共7页合成和系统生物技术（英文）

基　　金：supported by the National Natural Science Foundation of China(32122005 and 32370051)to Y.-L.D.

摘　　要：The biological signaling molecule nitric oxide(NO)has recently emerged as a metabolic precursor for the creation of microbial natural products with diversified structures and biological activities.Within the biosynthetic gene clusters(BGCs)of these compounds,genes associated with NO production pathways have been pinpointed.In this study,we employ a nitric oxide synthase(NOS)-guided genome mining strategy for the targeted discovery of NO-derived bacterial natural products and NO-utilizing biocatalysts.We show that a conserved NOS-containing BGC,distributed across several actinobacterial genomes,is responsible for the biosynthesis of lajollamycin,a unique nitro-tetraene-containing antibiotic whose biosynthetic mechanism remains elusive.Through a combination of in vivo and in vitro studies,we unveil the first cytochrome P450 enzyme capable of catalyzing olefin nitration in natural product biosynthesis.These results not only expand the current knowledge about biosynthetic nitration processes but also offer an efficient way for targeted identification of NO-utilizing metabolic pathways and novel nitrating biocatalysts.

关 键 词：Nitric oxide Genome mining BIOSYNTHESIS NITRATION CYTOCHROME P450 

分 类 号：O63[理学—高分子化学]