Metabolic engineering of Corynebacterium glutamicum ATCC13869 for l-valine production

• Overexpression of lrp1 in Corynebacterium glutamicum ATCC13869 increased l-valine production by 16-fold.
• Deletion of 3 key genes in C. glutamicum ATCC13869 increased l-valine production by 44-fold.
• Expression of 6 genes in the 3-gene deletion mutant further increased l-valine production.
• The final strain could produce 0.47 mol of l-valine from 1 mol of glucose.

In this study, an l-valine-producing strain was developed from Corynebacterium glutamicum ATCC13869 through deletion of the three genes aceE, alaT and ilvA combined with the overexpression of six genes ilvB, ilvN, ilvC, lrp1, brnF and brnE. Overexpression of lrp1 alone increased l-valine production by 16-fold. Deletion of the aceE, alaT and ilvA increased l-valine production by 44-fold. Overexpression of the six genes ilvB, ilvN, ilvC, lrp1, brnE and brnF in the triple deletion mutant WCC003 further increased l-valine production. The strain WCC003/pJYW-4-ilvBNC1-lrp1-brnFE produced 243 mM l-valine in flask cultivation and 437 mM (51 g/L) l-valine in fed-batch fermentation and lacked detectable amino-acid byproduct such as l-alanine and l-isoleucine that are usually found in the fermentation of l-valine-producing C. glutamicum.