Metabolic engineering of Corynebacterium glutamicum for enhanced production of 5-aminovaleric acid

Shin, Jae Ho, Park, Seok Hyun, Oh, Young Hoon, Choi, Jae Woong, Lee, Moon Hee, Cho, Jae Sung, Jeong, Ki Jun, Joo, Jeong Chan, Yu, James, Park, Si Jae and Lee, Sang Yup (2016) Metabolic engineering of Corynebacterium glutamicum for enhanced production of 5-aminovaleric acid. Microbial Cell Factories, 15 1: 174. doi:10.1186/s12934-016-0566-8

Author Shin, Jae Ho
Park, Seok Hyun
Oh, Young Hoon
Choi, Jae Woong
Lee, Moon Hee
Cho, Jae Sung
Jeong, Ki Jun
Joo, Jeong Chan
Yu, James
Park, Si Jae
Lee, Sang Yup
Title Metabolic engineering of Corynebacterium glutamicum for enhanced production of 5-aminovaleric acid
Journal name Microbial Cell Factories   Check publisher's open access policy
ISSN 1475-2859
Publication date 2016-10-07
Sub-type Article (original research)
DOI 10.1186/s12934-016-0566-8
Open Access Status DOI
Volume 15
Issue 1
Start page 174
Total pages 13
Place of publication London, United Kingdom
Publisher BioMed Central
Abstract 5-Aminovaleric acid (5AVA) is an important five-carbon platform chemical that can be used for the synthesis of polymers and other chemicals of industrial interest. Enzymatic conversion of L-lysine to 5AVA has been achieved by employing lysine 2-monooxygenase encoded by the davB gene and 5-aminovaleramidase encoded by the davA gene. Additionally, a recombinant Escherichia coli strain expressing the davB and davA genes has been developed for bioconversion of L-lysine to 5AVA. To use glucose and xylose derived from lignocellulosic biomass as substrates, rather than L-lysine as a substrate, we previously examined direct fermentative production of 5AVA from glucose by metabolically engineered E. coli strains. However, the yield and productivity of 5AVA achieved by recombinant E. coli strains remain very low. Thus, Corynebacterium glutamicum, a highly efficient L-lysine producing microorganism, should be useful in the development of direct fermentative production of 5AVA using L-lysine as a precursor for 5AVA. Here, we report the development of metabolically engineered C. glutamicum strains for enhanced fermentative production of 5AVA from glucose.

Various expression vectors containing different promoters and origins of replication were examined for optimal expression of Pseudomonas putida davB and davA genes encoding lysine 2-monooxygenase and delta-aminovaleramidase, respectively. Among them, expression of the C. glutamicum codon-optimized davA gene fused with His-Tag at its N-Terminal and the davB gene as an operon under a strong synthetic H promoter (plasmid p36davAB3) in C. glutamicum enabled the most efficient production of 5AVA. Flask culture and fed-batch culture of this strain produced 6.9 and 19.7 g/L (together with 11.9 g/L glutaric acid as major byproduct) of 5AVA, respectively. Homology modeling suggested that endogenous gamma-aminobutyrate aminotransferase encoded by the gabT gene might be responsible for the conversion of 5AVA to glutaric acid in recombinant C. glutamicum. Fed-batch culture of a C. glutamicum gabT mutant-harboring p36davAB3 produced 33.1 g/L 5AVA with much reduced (2.0 g/L) production of glutaric acid.

Corynebacterium glutamicum was successfully engineered to produce 5AVA from glucose by optimizing the expression of two key enzymes, lysine 2-monooxygenase and delta-aminovaleramidase. In addition, production of glutaric acid, a major byproduct, was significantly reduced by employing C. glutamicum gabT mutant as a host strain. The metabolically engineered C. glutamicum strains developed in this study should be useful for enhanced fermentative production of the novel C5 platform chemical 5AVA from renewable resources.
Keyword 5-Aminovaleric acid
Corynebacterium glutamicum
Glutaric acid
Metabolic engineering
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Australian Institute for Bioengineering and Nanotechnology Publications
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Citation counts: TR Web of Science Citation Count  Cited 9 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 02 May 2018, 14:14:45 EST