Developing the E. coli platform for efficient production of UMP-derived chemicals

IF 6.8 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
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
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Abstract

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.

开发高效生产 UMP 衍生化学品的大肠杆菌平台。
5-甲基尿苷(5-MU)是工业合成多种抗病毒药物的重要中间体,然而,在过去几十年中,它的获取绝大多数依赖于化学和酶法策略。在这里,我们首次实现了在大肠杆菌中通过双酶级联(UMP 5-甲基化酶和磷酸酶)设计的人工途径高效生产 5-MU。更重要的是,我们通过对多种策略的系统评估,设计了大肠杆菌细胞工厂,以提高 5-MU 的产量。作为概念验证,我们进一步开发了一种无抗生素发酵策略,在大肠杆菌 MB229(ΔthyA 菌株)中实现了 5-MU 的产量(10.71 克/升)。值得注意的是,我们还建立了一个多功能、稳健的平台,利用改造后的大肠杆菌高效生产多种 UMP 衍生化学品。这项研究为未来将大肠杆菌工程化为合成生物学平台,加速获取 UMP 衍生的多样化化学物质铺平了道路。
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来源期刊
Metabolic engineering
Metabolic engineering 工程技术-生物工程与应用微生物
CiteScore
15.60
自引率
6.00%
发文量
140
审稿时长
44 days
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.
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