Jan van Ooyen and Stephan Noack have contributed equally to this work.
Article first published online: 22 MAR 2012
Copyright © 2012 Wiley Periodicals, Inc.
Biotechnology and Bioengineering
Volume 109, Issue 8, pages 2070–2081, August 2012
How to Cite
van Ooyen, J., Noack, S., Bott, M., Reth, A. and Eggeling, L. (2012), Improved L-lysine production with Corynebacterium glutamicum and systemic insight into citrate synthase flux and activity. Biotechnol. Bioeng., 109: 2070–2081. doi: 10.1002/bit.24486
The authors have no conflict of interest to declare.
- Issue published online: 18 JUN 2012
- Article first published online: 22 MAR 2012
- Accepted manuscript online: 5 MAR 2012 10:27AM EST
- Manuscript Accepted: 22 FEB 2012
- Manuscript Revised: 15 FEB 2012
- Manuscript Received: 22 DEC 2011
- JvO. Grant Number: 0313704
- citrate synthase;
- metabolite pools;
- in vivo kinetics;
- metabolite production
We here developed a series of Corynebacterium glutamicum strains with gradual decreased specific citrate synthase (CS) activity and quantified in a multifaceted approach the consequences of residual activity on the transcriptome, metabolome, and fluxome level as well as on L-lysine formation and growth. We achieved an intended gradual L-lysine yield increase and recognized and overcame further new limitations in the L-lysine biosynthesis pathway to result in a strain with the highest yield reported so far when assayed under comparable conditions. As a non-intended outcome, a detailed flux analysis revealed an almost constant flux through CS at 10% remaining CS activity, whereas the metabolome data revealed an increase in the oxaloacetate and acetyl-CoA concentrations. Hence reduced CS activity is apparently efficiently buffered by increased concentrations of CS substrates, implying a certain robustness of the central metabolism in response of the imposed gene expressions. Biotechnol. Bioeng. 2012; 109:2070–2081. © 2012 Wiley Periodicals, Inc.