High-level production of L-valine in Escherichia coli using multi-modular engineering. (September 2022)

• Record Type: Journal Article
• Authors: Hao, Yanan; Pan, Xuewei; Xing, Rufan; You, Jiajia; Hu, Mengkai; Liu, Zhifei; Li, Xiangfei; Xu, Meijuan; Rao, Zhiming
• Is Part Of: Bioresource technology. Volume 359(2022)
• Publication Date: 2022-09
• Subjects: Escherichia coli -- L-valine -- Metabolic engineering -- Transcription factor -- Cofactor 1; Biomass -- Periodicals; Biomass energy -- Periodicals; Bioremediation -- Periodicals; Agricultural wastes -- Periodicals; Factory and trade waste -- Periodicals; Organic wastes -- Periodicals; Bioénergie -- Périodiques; Déchets agricoles -- Périodiques; Déchets industriels -- Périodiques; Déchets organiques -- Périodiques; Déchets (Combustible) -- Périodiques; 662.88
• DOI: 10.1016/j.biortech.2022.127461
• Languages: English
• ISSNs: 0960-8524

Abstract

Graphical abstract: Highlights: ARTP mutagenesis was applied for constructing L-valine-producing strain. Transcription factors associated with L-valine biosynthesis were investigated. Modification of PdhR and RpoS increased the production of L-valine. Entner-Doudoroff pathway from Zymomonas mobilis promoted NADPH regeneration. The titer of L-valine reached 92 g/L in 5 L bioreactor. Abstract: L-valine is a valuable amino acid in mammals that is used as the main component of feed additives. The low efficiency of the fermentation titer limits the industrial application of L-valine. Here, an L-valine-producing strain of Escherichia coli was obtained using a multi-modular strategy. Initially, a chassis strain was generated by mutagenesis and high-throughput screening. The L-valine biosynthetic pathway and transport module were modified to improve the L-valine titer. Subsequently, the transcription factors associated with L-valine biosynthesis were investigated. Overexpression of PdhR and inhibition of the expression of RpoS promoted L-valine synthesis. Finally, the NADPH supply was enhanced after the introduction of the heterologous Entner-Doudoroff (ED) pathway from Zymomonas mobilis . The strain VAL38 produced 92 g/L L-valine in a 5-L bioreactor with a yield of 0.34 g/g glucose. This strategy is provided as a reference for improving the production performance of cell factories for L-valine and its derivatives.