Le Yu , Yaojie Gao , Yuanyuan He , Yang Liu , Jianning Shen , Han Liang , Rong Gong , He Duan , Neil P.J. Price , Xuemin Song , Zixin Deng , Wenqing Chen
{"title":"开发高效生产 UMP 衍生化学品的大肠杆菌平台。","authors":"Le Yu , Yaojie Gao , Yuanyuan He , Yang Liu , Jianning Shen , Han Liang , Rong Gong , He Duan , Neil P.J. Price , Xuemin Song , Zixin Deng , Wenqing Chen","doi":"10.1016/j.ymben.2024.03.004","DOIUrl":null,"url":null,"abstract":"<div><p>5-Methyluridine (5-MU) is a prominent intermediate for industrial synthesis of several antiviral-drugs, however, its availability over the past decades has overwhelmingly relied on chemical and enzymatic strategies. Here, we have realized efficient production of 5-MU in <em>E. coli,</em> for the first time, <em>via</em> a designer artificial pathway consisting of a two-enzyme cascade (UMP 5-methylase and phosphatase). More importantly, we have engineered the <em>E. coli</em> cell factory to boost 5-MU production by systematic evaluation of multiple strategies, and as a proof of concept, we have further developed an antibiotic-free fermentation strategy to realize 5-MU production (10.71 g/L) in <em>E. coli</em> MB229 (a <em>ΔthyA</em> strain). Remarkably, we have also established a versatile and robust platform with exploitation of the engineered <em>E. coli</em> for efficient production of diversified UMP-derived chemicals. This study paves the way for future engineering of <em>E. coli</em> as a synthetic biology platform for acceleratively accessing UMP-derived chemical diversities.</p></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":null,"pages":null},"PeriodicalIF":6.8000,"publicationDate":"2024-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Developing the E. coli platform for efficient production of UMP-derived chemicals\",\"authors\":\"Le Yu , Yaojie Gao , Yuanyuan He , Yang Liu , Jianning Shen , Han Liang , Rong Gong , He Duan , Neil P.J. Price , Xuemin Song , Zixin Deng , Wenqing Chen\",\"doi\":\"10.1016/j.ymben.2024.03.004\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>5-Methyluridine (5-MU) is a prominent intermediate for industrial synthesis of several antiviral-drugs, however, its availability over the past decades has overwhelmingly relied on chemical and enzymatic strategies. Here, we have realized efficient production of 5-MU in <em>E. coli,</em> for the first time, <em>via</em> a designer artificial pathway consisting of a two-enzyme cascade (UMP 5-methylase and phosphatase). More importantly, we have engineered the <em>E. coli</em> cell factory to boost 5-MU production by systematic evaluation of multiple strategies, and as a proof of concept, we have further developed an antibiotic-free fermentation strategy to realize 5-MU production (10.71 g/L) in <em>E. coli</em> MB229 (a <em>ΔthyA</em> strain). Remarkably, we have also established a versatile and robust platform with exploitation of the engineered <em>E. coli</em> for efficient production of diversified UMP-derived chemicals. This study paves the way for future engineering of <em>E. coli</em> as a synthetic biology platform for acceleratively accessing UMP-derived chemical diversities.</p></div>\",\"PeriodicalId\":18483,\"journal\":{\"name\":\"Metabolic engineering\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.8000,\"publicationDate\":\"2024-03-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Metabolic engineering\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1096717624000491\",\"RegionNum\":1,\"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":"Metabolic engineering","FirstCategoryId":"5","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1096717624000491","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
Developing the E. coli platform for efficient production of UMP-derived chemicals
5-Methyluridine (5-MU) is a prominent intermediate for industrial synthesis of several antiviral-drugs, however, its availability over the past decades has overwhelmingly relied on chemical and enzymatic strategies. Here, we have realized efficient production of 5-MU in E. coli, for the first time, via a designer artificial pathway consisting of a two-enzyme cascade (UMP 5-methylase and phosphatase). More importantly, we have engineered the E. coli cell factory to boost 5-MU production by systematic evaluation of multiple strategies, and as a proof of concept, we have further developed an antibiotic-free fermentation strategy to realize 5-MU production (10.71 g/L) in E. coli MB229 (a ΔthyA strain). Remarkably, we have also established a versatile and robust platform with exploitation of the engineered E. coli for efficient production of diversified UMP-derived chemicals. This study paves the way for future engineering of E. coli as a synthetic biology platform for acceleratively accessing UMP-derived chemical diversities.
期刊介绍:
Metabolic Engineering (MBE) is a journal that focuses on publishing original research papers on the directed modulation of metabolic pathways for metabolite overproduction or the enhancement of cellular properties. It welcomes papers that describe the engineering of native pathways and the synthesis of heterologous pathways to convert microorganisms into microbial cell factories. The journal covers experimental, computational, and modeling approaches for understanding metabolic pathways and manipulating them through genetic, media, or environmental means. Effective exploration of metabolic pathways necessitates the use of molecular biology and biochemistry methods, as well as engineering techniques for modeling and data analysis. MBE serves as a platform for interdisciplinary research in fields such as biochemistry, molecular biology, applied microbiology, cellular physiology, cellular nutrition in health and disease, and biochemical engineering. The journal publishes various types of papers, including original research papers and review papers. It is indexed and abstracted in databases such as Scopus, Embase, EMBiology, Current Contents - Life Sciences and Clinical Medicine, Science Citation Index, PubMed/Medline, CAS and Biotechnology Citation Index.