LAUSR

BACKGROUND l-Leucine is one of important essential amino acids with multiple industrial applications, whose market requirements cannot be met because of the lower 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 was achieved under the optimized conditions, with the l-leucine yield and productivity of 0.25 g/g glucose and 0.59 g/L/h, respectively. CONCLUSIONS AND IMPLICATIONS These results represent a significant improvement in the l-leucine titer of C. glutamicum, indicating that the process possesses highly 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. This article is protected by copyright. All rights reserved.