Metabolic engineering of Corynebacterium glutamicum for the production of glutaric acid, a C5 dicarboxylic acid platform chemical

• Published in: Metabolic engineering Vol. 51; pp. 99 - 109
• Main Authors: Kim, Hee Taek, Khang, Tae Uk, Baritugo, Kei-Anne, Hyun, Sung Min, Kang, Kyoung Hee, Jung, Sol Hee, Song, Bong Keun, Park, Kyungmoon, Oh, Min-Kyu, Kim, Gi Bae, Kim, Hyun Uk, Lee, Sang Yup, Park, Si Jae, Joo, Jeong Chan
• Format: Journal Article
• Language: English
• Published: Belgium Elsevier Inc 01.01.2019
• Subjects: Codon optimization; Corynebacterium glutamicum; davTDBA; Fed-batch fermentation; Glutaric acid; His6-tag; L‐Lysine; davTDBA; Glutaric acid; Corynebacterium glutamicum; Fed-batch fermentation; L‐Lysine; His6-tag; Codon optimization; His-tag
• ISSN: 1096-7176; 1096-7184
• DOI: 10.1016/j.ymben.2018.08.007

Corynebacterium glutamicum was metabolically engineered for the production of glutaric acid, a C5 dicarboxylic acid that can be used as platform building block chemical for nylons and plasticizers. C. glutamicum gabT and gabD genes and Pseudomonas putida davT and davD genes encoding 5-aminovalerate transaminase and glutarate semialdehyde dehydrogenase, respectively, were examined in C. glutamicum for the construction of a glutaric acid biosynthesis pathway along with P. putida davB and davA genes encoding lysine 2-monooxygenase and delta-aminovaleramidase, respectively. The glutaric acid biosynthesis pathway constructed in recombinant C. glutamicum was engineered by examining strong synthetic promoters PH30 and PH36, C. glutamicum codon-optimized davTDBA genes, and modification of davB gene with an N-terminal His6-tag to improve the production of glutaric acid. It was found that use of N-terminal His6-tagged DavB was most suitable for the production of glutaric acid from glucose. Fed-batch fermentation using the final engineered C. glutamicum H30_GAHis strain, expressing davTDA genes along with davB fused with His6-tag at N-terminus could produce 24.5 g/L of glutaric acid with low accumulation of l-lysine (1.7 g/L), wherein 5-AVA accumulation was not observed during fermentation. •C. glutamicum strains were metabolically engineered for the production of glutaric acid.•Optimization of glutaric acid biosynthesis pathway could enhance glutaric acid production.•Recombinant C. glutamicum strains efficiently produced glutaric acid from glucose.•Fed-batch culture of recombinant C. glutamicum H30_GAHis supported high-level production of glutaric acid from glucose.