%0 Journal Article %1 vanOoyen2012Improved %A van Ooyen, Jan %A Noack, Stephan %A Bott, Michael %A Reth, Alexander %A Eggeling, Lothar %D 2012 %I Wiley Subscription Services, Inc., A Wiley Company %J Biotechnol. Bioeng. %K flux-analysis lysine metabolic-engineering %N 8 %P 2070--2081 %R 10.1002/bit.24486 %T Improved L-lysine production with Corynebacterium glutamicum and systemic insight into citrate synthase flux and activity %U http://dx.doi.org/10.1002/bit.24486 %V 109 %X 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. \copyright 2012 Wiley Periodicals, Inc.

@article{vanOoyen2012Improved, abstract = {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. {\copyright} 2012 Wiley Periodicals, Inc.}, added-at = {2018-12-02T16:09:07.000+0100}, author = {van Ooyen, Jan and Noack, Stephan and Bott, Michael and Reth, Alexander and Eggeling, Lothar}, biburl = {https://www.bibsonomy.org/bibtex/2660082dd508d09103e375abec4f8a539/karthikraman}, citeulike-article-id = {11726158}, citeulike-linkout-0 = {http://dx.doi.org/10.1002/bit.24486}, doi = {10.1002/bit.24486}, interhash = {691e9fde9eb820b7ee53b9016af8b0e1}, intrahash = {660082dd508d09103e375abec4f8a539}, journal = {Biotechnol. Bioeng.}, keywords = {flux-analysis lysine metabolic-engineering}, number = 8, pages = {2070--2081}, posted-at = {2012-11-19 06:53:05}, priority = {2}, publisher = {Wiley Subscription Services, Inc., A Wiley Company}, timestamp = {2018-12-02T16:09:07.000+0100}, title = {Improved L-lysine production with Corynebacterium glutamicum and systemic insight into citrate synthase flux and activity}, url = {http://dx.doi.org/10.1002/bit.24486}, volume = 109, year = 2012 }