Improvement of acetyl‐CoA supply and glucose utilization increases l‐leucine production in Corynebacterium glutamicum

Abstract Background l ‐Leucine is an important essential amino acid with multiple industrial applications, whose market requirements cannot be met because of the low productivity. Main Methods and Major Results In this study, a strain of Corynebacterium glutamicum with high l ‐leucine yield was constructed to enhance its acetyl‐CoA supply and glucose utilization. One copy of leuA under the control of a strong promoter was incorporated into the C. glutamicum genome. Then, acetyl‐CoA supply was increased by the integration of a terminator in front of gltA and by the heterogeneous overexpression of acetyl‐CoA synthetase (ACS) and deacetylase (CobB) derived from Escherichia coli . Next, the transcriptional regulator sugR was deleted to enhance glucose uptake via a phosphotransferase‐mediated route. In fed‐batch fermentation performed in a 5‐L reactor, l ‐leucine production of 40.11 ± 0.73 g L −1 was achieved under the optimized conditions, with an l ‐leucine yield and productivity of 0.25 g g −1 glucose and 0.59 g L −1 h −1 , respectively. Conclusions and Implications These results represent a significant improvement in the l ‐leucine production of C. glutamicum , indicating that the process possesses high potential for industrial application. These strategies can be also expanded to enable the production of other value‐added biochemicals derived from the intermediates of central carbon metabolism.