Efficient synthesis of L-methionine by engineering the one carbon module of <i>Escherichia coli</i>.

Bo Zhang; Ying Wang; Kun Niu; Zhiqiang Liu; Yuguo Zheng

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Efficient synthesis of L-methionine by engineering the one carbon module of Escherichia coli.

Author: Bo ZHANG ¹ ; Ying WANG ¹ ; Kun NIU ¹ ; Zhiqiang LIU ¹ ; Yuguo ZHENG ¹
Author Information

1. The National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals, Zhejiang University of Technology, Hangzhou 310014, Zhejiang, China.
Publication Type:Journal Article
Keywords: L-methionine; biosynthesis pathway; coordinated gene expression; fermentation engineering; metabolic engineering
MeSH: Humans; Methionine; Methylenetetrahydrofolate Reductase (NADPH2); Carbon; Cysteine; Escherichia coli/genetics*; Hydroxymethyl and Formyl Transferases; Carrier Proteins; Escherichia coli Proteins
From: Chinese Journal of Biotechnology 2023;39(8):3302-3317
CountryChina
Language:Chinese
Abstract: L-methionine, also known as L-aminomethane, is one of the eight essential amino acids required by the human body and has important applications in the fields of feed, medicine, and food. In this study, an L-methionine high-yielding strain was constructed using a modular metabolic engineering strategy based on the M2 strain (Escherichia coli W3110 ΔIJAHFEBC/PAM) previously constructed in our laboratory. Firstly, the production of one-carbon module methyl donors was enhanced by overexpression of methylenetetrahydrofolate reductase (methylenetetrahydrofolate reductase, MetF) and screening of hydroxymethyltransferase (GlyA) from different sources, optimizing the one-carbon module. Subsequently, cysteamine lyase (hydroxymethyltransferase, MalY) and cysteine internal transporter gene (fliY) were overexpressed to improve the supply of L-homocysteine and L-cysteine, two precursors of the one-carbon module. The production of L-methionine in shake flask fermentation was increased from 2.8 g/L to 4.05 g/L, and up to 18.26 g/L in a 5 L fermenter. The results indicate that the one carbon module has a significant impact on the biosynthesis of L-methionine, and efficient biosynthesis of L-methionine can be achieved through optimizing the one carbon module. This study may facilitate further improvement of microbial fermentation production of L-methionine.