Production of 4-hydroxybutyric acid by metabolically engineered Mannheimia succiniciproducens and its conversion to gamma-butyrolactone by acid treatment

Junho Bang, Sol Choi, KAIST, Hyun Uk Kim, KAIST, Won Jun Kim, KAIST Daeharkro 291, Daejeon, Republic of Korea
T: +82-42-350-5970, choi1209@kaist.ac.kr
Sang Yup Lee, KAIST
γ-Butyrolactone (GBL) is an important four carbon (C4) chemical, which has a wide range of industrial applications. GBL can be produced by acid treatment of 4-hydroxybutyric acid (4-HB), which is a derivative of succinic acid. Heterologous metabolic pathways were designed and established in succinic acid overproducing M. succiniciproducens LPK7 by the introduction of heterologous genes that encode succinyl-CoA synthetase, CoA-dependent succinate semialdehyde dehydrogenase and either 4-hydroxybutyrate dehydrogenase in LPK7 (p3S4CD) or succinate semialdehyde reductase in LPK7 (p3SYCD). Fed-batch cultures of LPK7 (p3S4CD) and LPK7 (p3SYCD) resulted in the production of 6.37 and 6.34 g/L of 4-HB, respectively. Finally, GBL was produced by acid treatment of the 4-HB obtained from the fermentation broth. This study demonstrates that 4- HB, and potentially other four carbon platform chemicals, can be produced by the engineered rumen bacterium M. succiniciproducens. [â??This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries from the Ministry of Science, ICT and Future Planning (MSIP) through the National Research Foundation (NRF) of Korea (NRF-2012-C1AAA001-

2012M1A2A2026556).]