Efficient biosynthesis of α‐aminoadipic acid via lysine catabolism in Escherichia coli. Issue 1 (20th October 2022)

• Record Type: Journal Article
• Authors: Zhang, Yu; An, Ning; Zhao, Yan; Li, Xueqi; Shen, Xiaolin; Wang, Jia; Sun, Xinxiao; Yuan, Qipeng
• Is Part Of: Biotechnology and bioengineering. Volume 120:Issue 1(2023)
• Page Start: 312
• Page End: 317
• Publication Date: 2022-10-20
• Subjects: α‐aminoadipic acid -- efflux -- Escherichia coli -- lysine degradation -- metabolic engineering; Biotechnology -- Periodicals; Bioengineering -- Periodicals; 660.6
• DOI: 10.1002/bit.28256
• Languages: English
• ISSNs: 0006-3592

Abstract

Abstract: α‐Aminoadipic acid (AAA) is a nonproteinogenic amino acid with potential applications in pharmaceutical, chemical and animal feed industries. Currently, AAA is produced by chemical synthesis, which suffers from high cost and low production efficiency. In this study, we engineered Escherichia coli for high‐level AAA production by coupling lysine biosynthesis and degradation pathways. First, the lysine‐α‐ketoglutarate reductase and saccharopine dehydrogenase from Saccharomyces cerevisia e and α‐aminoadipate‐δ‐semialdehyde dehydrogenase from Rhodococcus erythropolis were selected by in vitro enzyme assays for pathway assembly. Subsequently, lysine supply was enhanced by blocking its degradation pathway, overexpressing key pathway enzymes and improving nicotinamide adenine dineucleotide phosphate (NADPH) regeneration. Finally, a glutamate transporter from Corynebacterium glutamicum was introduced to elevate AAA efflux. The final strain produced 2.94 and 5.64 g/L AAA in shake flasks and bioreactors, respectively. This work provides an efficient and sustainable way for AAA production. Abstract : Escherichia coli was engineered for α‐aminoadipic acid (AAA) biosynthesis by coupling lysine biosynthesis and degradation pathways. The production efficiency was improved by blocking lysine degradation pathway, enhancing lysine biosynthetic flux, improving NADPH supply and elevating AAA efflux. This work demonstrates a novel and efficient bioprocess for production of AAA and its derivatives.