First, the TCA cycle, glyoxylate shunt and some adjacent reactions of

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First, the TCA cycle, glyoxylate shunt and some adjacent reactions of

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Elementary-Modes Analysis of Lysine Production in Corynebacterium glutamicum and Escherichia coliStefan Schuster and Axel von KampFriedrich Schiller University Jena, Dept. of BioinformaticsErnst-Abbe-Pl. 2, 07743 Jenaemail: (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.

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 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, 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.

Chemical structure of lysine

First reaction scheme

Pathway with the best yield

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

[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.

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.