TY - JOUR
T1 - Metabolic engineering of Corynebacterium glutamicum for highly selective production of 5-hydroxyvaleric acid
AU - Sohn, Yu Jung
AU - Kim, Hee Taek
AU - Kang, Minsoo
AU - Son, Jina
AU - Park, Kyungmoon
AU - Jeong, Ki Jun
AU - Lee, Sang Yup
AU - Joo, Jeong Chan
AU - Park, Si Jae
N1 - Publisher Copyright:
© 2025 International Metabolic Engineering Society
PY - 2025/7
Y1 - 2025/7
N2 - The biosynthesis of 5-hydroxyvaleric acid (5-HV) from glucose via the l-lysine degradation pathway cocurrently generates by-products, including l-lysine, 5-aminovaleric acid (5-AVA), and glutaric acid (GTA), which are closely interconnected with the 5-HV biosynthesis pathway. This study focuses on developing a highly selective 5-HV production system in Corynebacterium glutamicum. Initial strategies, such as using sorbitol as a co-substrate, deleting the endogenous GTA biosynthesis pathway, and incorporating a GTA recycling system, were insufficient to achieve selectivity. To address this, a combination of strategies was implemented, including deletion of the endogenous GTA biosynthesis pathway, incorporation of a GTA recycling pathway, removal of the l-lysine exporter gene (lysE), and integration of a l-lysine conversion module. These modifications synergistically enhanced 5-HV selectivity. The final engineered strain, which lacked lysE and gabD2 genes and overexpressed the 5-HV biosynthesis and GTA recycling modules, achieved 88.23 g/L of 5-HV in fed-batch fermentation. By-product levels were significantly reduced to 3.28 g/L of GTA, 1.16 g/L of 5-AVA, and no detectable l-lysine. With this highly selective 5-HV biosynthesis system, δ-valerolactone (DVL) was synthesized via acid treatment of microbially produced 5-HV, achieving a 65% conversion efficiency. This approach presents a more environmentally friendly and sustainable method for producing DVL, a valuable C5 solvent with industrial applications.
AB - The biosynthesis of 5-hydroxyvaleric acid (5-HV) from glucose via the l-lysine degradation pathway cocurrently generates by-products, including l-lysine, 5-aminovaleric acid (5-AVA), and glutaric acid (GTA), which are closely interconnected with the 5-HV biosynthesis pathway. This study focuses on developing a highly selective 5-HV production system in Corynebacterium glutamicum. Initial strategies, such as using sorbitol as a co-substrate, deleting the endogenous GTA biosynthesis pathway, and incorporating a GTA recycling system, were insufficient to achieve selectivity. To address this, a combination of strategies was implemented, including deletion of the endogenous GTA biosynthesis pathway, incorporation of a GTA recycling pathway, removal of the l-lysine exporter gene (lysE), and integration of a l-lysine conversion module. These modifications synergistically enhanced 5-HV selectivity. The final engineered strain, which lacked lysE and gabD2 genes and overexpressed the 5-HV biosynthesis and GTA recycling modules, achieved 88.23 g/L of 5-HV in fed-batch fermentation. By-product levels were significantly reduced to 3.28 g/L of GTA, 1.16 g/L of 5-AVA, and no detectable l-lysine. With this highly selective 5-HV biosynthesis system, δ-valerolactone (DVL) was synthesized via acid treatment of microbially produced 5-HV, achieving a 65% conversion efficiency. This approach presents a more environmentally friendly and sustainable method for producing DVL, a valuable C5 solvent with industrial applications.
KW - 5-Hydroxyvaleric acid
KW - Corynebacterium glutamicum
KW - Glutaric acid recycling
KW - Sustainable bioproduction
KW - l-Lysine degradation pathway
KW - δ-valerolactone
UR - https://www.scopus.com/pages/publications/86000366973
U2 - 10.1016/j.ymben.2025.03.002
DO - 10.1016/j.ymben.2025.03.002
M3 - Article
C2 - 40054728
AN - SCOPUS:86000366973
SN - 1096-7176
VL - 90
SP - 33
EP - 42
JO - Metabolic Engineering
JF - Metabolic Engineering
ER -