RETRACTED ARTICLE: Systems engineering of Escherichia coli for high-level glutarate production from glucose

Zhilan Zhang, Ruyin Chu, Wanqing Wei, Wei Song, Chao Ye, Xiulai Chen, Jing Wu, Liming Liu and Cong Gao ()
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Zhilan Zhang: Jiangnan University
Ruyin Chu: Jiangnan University
Wanqing Wei: Jiangnan University
Wei Song: Jiangnan University
Chao Ye: Nanjing Normal University
Xiulai Chen: Jiangnan University
Jing Wu: Jiangnan University
Liming Liu: Jiangnan University
Cong Gao: Jiangnan University

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Glutarate is a key monomer in polyester and polyamide production. The low efficiency of the current biosynthetic pathways hampers its production by microbial cell factories. Herein, through metabolic simulation, a lysine-overproducing E. coli strain Lys5 is engineered, achieving titer, yield, and productivity of 195.9 g/L, 0.67 g/g glucose, and 5.4 g/L·h, respectively. Subsequently, the pathway involving aromatic aldehyde synthase, monoamine oxidase, and aldehyde dehydrogenase (AMA pathway) is introduced into E. coli Lys5 to produce glutarate from glucose. To enhance the pathway’s efficiency, rational mutagenesis on the aldehyde dehydrogenase is performed, resulting in the development of variant Mu5 with a 50-fold increase in catalytic efficiency. Finally, a glutarate tolerance gene cbpA is identified and genomically overexpressed to enhance glutarate productivity. With enzyme expression optimization, the glutarate titer, yield, and productivity of E. coli AMA06 reach 88.4 g/L, 0.42 g/g glucose, and 1.8 g/L·h, respectively. These findings hold implications for improving glutarate biosynthesis efficiency in microbial cell factories.

Date: 2024
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DOI: 10.1038/s41467-024-45448-z

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