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

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

Metabolic Engineering 2024

https://www.sciencedirect.com/science/article/pii/S1096717624000491

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.