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

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
Metabolic engineering 2019 v.51 pp. 99-109
Corynebacterium glutamicum, Pseudomonas putida, batch fermentation, biosynthesis, genes, glucose, glutaric acid, lysine, metabolic engineering, nylon, plasticizers
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.