Elementary-Modes Analysis of Lysine Production
in Corynebacterium glutamicum and Escherichia coli
Stefan Schuster and Axel von Kamp
Friedrich Schiller University Jena, Dept. of Bioinformatics
Ernst-Abbe-Pl. 2, 07743 Jena
email: (schuster, kamp)@minet.uni-jena.de
Introduction
Elementary (flux) modes serve as a mathematical formalization of
metabolic pathways and describe potential simple flux distributions in
metabolic networks at steady state [1].
Here, we apply this method to finding the potential pathways and
associated molar yields in lysine production in C. glutamicum and E.
coli.
The essential amino acid, lysine is of great technological interest.
Chemical structure of lysine
First reaction scheme
Pathway with the best yield
Second reaction scheme
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 carboxylating 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, and
NADP/NADPH are here internal.
This scheme gives rise to 36 elem. modes
producing lysine [4]. 2 modes only use
glucose as a substrate (yield: ¾), five
modes only use acetate, and 29 use both.
The optimal lysine over glucose yield of ¾ coincides with earlier
results obtained by metabolite balancing in [3]. It is understandable
that the yield is lower than when ATP and ADP are external (cf.
first reaction scheme) because part of the glucose is needed for
synthesizing ATP. The optimal lysine over acetate yield is ¼.
References
First, the TCA cycle, glyoxylate shunt and some adjacent reactions of
amino acid metabolism in E. coli are considered. The carbon source
2-phosphoglycerate (PG), CO2, NH3, the produced amino acids and all
cofactors 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.
[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.