Article Open Access

Hydroxybenzoic Acid Production Using Metabolically Engineered Corynebacterium glutamicum

Synthetic Biology and Engineering. 2023, 1(2), 10010;
Misa Doke 1    Mayumi Kishida 1    Yuuki Hirata 1    Mariko Nakano 1    Mayo Horita 1    Daisuke Nonaka 1    Yutaro Mori 1    Ryosuke Fujiwara 2    Akihiko Kondo 2,3    Shuhei Noda 3,4    Tsutomu Tanaka 1 *   
Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 11 Rokkodai, Nada, Kobe 657-8501, Japan
RIKEN Center for Sustainable Resource Science, 1722 Suehirocho, Tsurumiku, Yokohama, Kanagawa 230‑0045, Japan
Graduate School of Science, Technology, and Innovation, Kobe University, 1-1, Rokkodai, Nada, Kobe 657-8501, Japan
Japan Science and Technology Agency (JST), PRESTO 4-1-8, Honcho, Kawaguchi-shi, Saitama 332-0012 Japan
Authors to whom correspondence should be addressed.

Received: 30 May 2023    Accepted: 14 Jul 2023    Published: 19 Jul 2023   


Hydroxybenzoic acids (HBAs), including 4-HBA, 3-HBA, and 2-HBA, are valuable platform chemicals for production of commodity materials and fine chemicals. Herein, we employed metabolic engineering techniques to enhance the production of these HBAs in Corynebacterium glutamicum ATCC 13032. Our approach augmented the shikimate pathway and eliminated genes associated with HBA degradation, particularly phenol 2-monooxygenase encoded by cg2966. Increased titers of 3-HBA and 4-HBA were achieved via selection of suitable promoters for 3-hydroxybenzoate synthase and chorismate pyruvate lyase. A tac-M1 promoter was suitable for chorismate pyruvate lyase expression and 8.3 g/L of 4-HBA production was achieved. Efficient production of 2-HBA was enabled by maintaining a balanced expression of isochorismate synthase and isochorismate pyruvate lyase. Consequently, strains KSD5-tacM1-H and KSD5-J2-PE exhibited production levels of 19.2 g/L of 3-HBA and 12.9 g/L of 2-HBA, respectively, using 1 L jar fermenter containing 80 g/L of glucose. Therefore, this engineered strain platform holds significant potential for production of other valuable products derived from chorismate.


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