Elementary-Modes Analysis of Lysine Production in Corynebacterium glutamicum and Escherichia coli

Stefan Schuster and Axel von KampFriedrich Schiller University Jena, Dept. of Bioinformatics

Ernst-Abbe-Pl. 2, 07743 Jenaemail: (schuster, kamp)@minet.uni-jena.de

First, the TCA cycle, glyoxylate shunt and some adjacent reactions of amino acid metabolism in E. coli are considered. The carbon source2-phosphoglycerate (PG), CO2, NH3, the produced amino acids and allcofactors such as ATP, ADP etc. are considered “external”. For this scheme, we computed, by the program METATOOL, 14 elementary modes, four of them producing lysine [2]. Molar lysine over glucose yields: 1, 2/3, 2/3 and ½.

Lysine production in C. glutamicum, based on [3]. Here, enzymes belonging to the same enzyme subset have been lumped. In addition to E. coli, the malic enzyme and the carboxyl-ating and decarboxylating enzymes linking Pyr with OAA are included.External metabolites: lysine, acetate, glucose, NAD/NADH, O2, CO2 and NH3. By contrast, the cofactors ATP/ADP, andNADP/NADPH are here internal.This scheme gives rise to 36 elem. modesproducing lysine [4]. 2 modes only use glucose as a substrate (yield: ¾), five modes only use acetate, and 29 use both.Pathway with the best yield

Second reaction schemeIntroductionElementary (flux) modes serve as a mathematical formalization ofmetabolic pathways and describe potential simple flux distributions inmetabolic networks at steady state [1].Here, we apply this method to finding the potential pathways andassociated molar yields in lysine production in C. glutamicum and E. coli.The essential amino acid, lysine is of great technological interest.

References[1] S. Schuster, T. Dandekar, D.A. Fell (1999) Trends Biotechnol. 17 53-60.[2] S. Schuster (2004) In: Metabolic Engineering in the Post Genomic Era (B.N. Kholodenko and H.V. Westerhoff, eds) Horizon Scientific, Wymondham, pp. 181-208.[3] A.A. de Graaf (2000) In Bioreaction Engineering, Modelling and Control (ed. K.B. Schügerl, K. H.), pp. 506-555. Springer, New York.[4] S. Schuster, A. von Kamp, M. Pachkov (2005) In: Metabolomics, Methods and Protocols (W. Weckwerth, ed.) Humana Press, Totowa (NJ), in press.

The optimal lysine over glucose yield of ¾ coincides with earlierresults obtained by metabolite balancing in [3]. It is understandablethat the yield is lower than when ATP and ADP are external (cf. first reaction scheme) because part of the glucose is needed forsynthesizing ATP. The optimal lysine over acetate yield is ¼.

First reaction scheme

Chemical structure of lysine