title: Improved L-lysine production with Corynebacterium glutamicum and systemic insight into citrate synthase flux and activity.
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.
authors.affiliation: Institute of Bio- and Geosciences, Biotechnology, Systemic Microbiology, Forschungszentrum Jülich GmbH, Jülich, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: van Ooyen
authors.forename: Stephan
authors.initials: S
authors.lastname: Noack
authors.forename: Michael
authors.initials: M
authors.lastname: Bott
authors.forename: Alexander
authors.initials: A
authors.lastname: Reth
authors.forename: Lothar
authors.initials: L
authors.lastname: Eggeling
mesh_terms: D002950:Citrate (si)-Synthase / Q000235:genetics / Q000378:metabolism*; D048230:Corynebacterium glutamicum / Q000201:enzymology* / Q000378:metabolism*; D015870:Gene Expression; D008239:Lysine / Q000096:biosynthesis*; D055442:Metabolome; D059467:Transcriptome
chemical_list: D002950:Citrate (si)-Synthase; D008239:Lysine