Hu Li , Wei Li , Kaihui Song , Yu Liu , Guiyun Zhao , Yi-Ling Du
{"title":"一氧化氮合成酶引导的基因组挖掘发现了细菌特殊代谢中的烯烃硝化细胞色素 P450 酶","authors":"Hu Li , Wei Li , Kaihui Song , Yu Liu , Guiyun Zhao , Yi-Ling Du","doi":"10.1016/j.synbio.2024.01.005","DOIUrl":null,"url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":null,"pages":null},"PeriodicalIF":4.4000,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X2400005X/pdfft?md5=a6bd2203eec7a9e46938bd177f8fbe54&pid=1-s2.0-S2405805X2400005X-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Nitric oxide synthase-guided genome mining identifies a cytochrome P450 enzyme for olefin nitration in bacterial specialized metabolism\",\"authors\":\"Hu Li , Wei Li , Kaihui Song , Yu Liu , Guiyun Zhao , Yi-Ling Du\",\"doi\":\"10.1016/j.synbio.2024.01.005\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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.</p></div>\",\"PeriodicalId\":22148,\"journal\":{\"name\":\"Synthetic and Systems Biotechnology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.4000,\"publicationDate\":\"2024-01-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2405805X2400005X/pdfft?md5=a6bd2203eec7a9e46938bd177f8fbe54&pid=1-s2.0-S2405805X2400005X-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Synthetic and Systems Biotechnology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2405805X2400005X\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Synthetic and Systems Biotechnology","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2405805X2400005X","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
Nitric oxide synthase-guided genome mining identifies a cytochrome P450 enzyme for olefin nitration in bacterial specialized metabolism
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.
期刊介绍:
Synthetic and Systems Biotechnology aims to promote the communication of original research in synthetic and systems biology, with strong emphasis on applications towards biotechnology. This journal is a quarterly peer-reviewed journal led by Editor-in-Chief Lixin Zhang. The journal publishes high-quality research; focusing on integrative approaches to enable the understanding and design of biological systems, and research to develop the application of systems and synthetic biology to natural systems. This journal will publish Articles, Short notes, Methods, Mini Reviews, Commentary and Conference reviews.