Metabolic engineering of Corynebacterium glutamicum ATCC13032 to produce S-adenosyl-l-methionine

• Four genes thrB, metB, mcbR and Ncgl2640 were deleted in C. glutamicum ATCC13032.
• Strain HW104 (ATCC13032 ΔthrB ΔmetB ΔmcbR ΔNcg l2640) can accumulate SAM.
• Six genes metK, vgb, lysCm, homm, metX and metY were overexpressed in HW104.
• HW104/pJYW-4- metK-vgb could accumulate 196.7 mg/L SAM after 48 h cultivation.
• SAM production in HW104/pJYW-4- metK-vgb does not need addition of l-methionine.

As an important biological methyl group donor, S-adenosyl-l-methionine is used as nutritional supplement or drug for various diseases, but bacterial strains that can efficiently produce S-adenosyl-l-methionine are not available. In this study, Corynebacterium glutamicum strain HW104 which can accumulate S-adenosyl-l-methionine was constructed from C. glutamicum ATCC13032 by deleting four genes thrB, metB, mcbR and Ncgl2640, and six genes metK, vgb, lysCm, homm, metX and metY were overexpressed in HW104 in different combinations, forming strains HW104/pJYW-4-metK-vgb, HW104/pJYW-4-SAM2C-vgb, HW104/pJYW-4-metK-vgb-metYX, and HW104/pJYW-4-metK-vgb-metYX-homm-lysCm. Fermentation experiments showed that HW104/pJYW-4-metK-vgb produced more S-adenosyl-l-methionine than other strains, and the yield achieved 196.7 mg/L (12.15 mg/g DCW) after 48 h. The results demonstrate the potential application of C. glutamicum for production of S-adenosyl-l-methionine without addition of l-methionine.