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. 2010 Dec;4(4):281-91.
doi: 10.1007/s11693-011-9073-8. Epub 2011 Feb 22.

Phenotypic characterization of Corynebacterium glutamicum using elementary modes towards synthesis of amino acids

Devesh Radhakrishnan, Meghna Rajvanshi, K V Venkatesh

Phenotypic characterization of Corynebacterium glutamicum using elementary modes towards synthesis of amino acids

Devesh Radhakrishnan et al. Syst Synth Biol. 2010 Dec.

Abstract

Elementary flux mode (EFM) analysis is a powerful tool to represent the metabolic network structure and can be further utilized for flux analysis. The method enables characterization and quantification of feasible phenotypes in microbes. EFM analysis was employed to characterize the phenotype of Corynebacterium glutamicum to yield various amino acids. The metabolic network of C. glutamicum yielded 62 elementary modes by incorporating the accumulation of amino acids namely, lysine, alanine, valine, glutamine and glutamate. The analysis also allowed us to compute the maximum theoretical yield for the synthesis of various amino acids. These 62 elementary modes were further used to obtain optimal phenotypic space towards accumulation of biomass and lysine. The study indicated that the optimal solution space from 62 elementary modes forms a super space which incorporates various mutants including lysine producing strain of C. glutamicum. The analysis was also extended to obtain sensitivity of the network to variation in the stoichiometry of NADP in the definition of biomass.

Electronic supplementary material: The online version of this article (doi:10.1007/s11693-011-9073-8) contains supplementary material, which is available to authorized users.

Keywords: Corynebacterium glutamicum; Elementary mode analysis; Flux analysis; Metabolic network; Optimal phenotypic space; Stoichiometry.

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Figures

Fig. 1
Fig. 1
Graphical representation of selected elementary modes. These are the modes which give maximum theoretical yield of the metabolite produced by them. Active reactions in the mode are shown with solid lines. Number assigned to the mode is same as given in the Electronic Supplementary Material 1
Fig. 2
Fig. 2
Optimal phenotypic spaces using 62 modes for C. glutamicum: (a) maximization of biomass and (b) maximization of lysine. Three constraints glucose, O2 and NH3 were specified in each case. Circle on the plots shows maximum feasible yield of biomass (115.7) or lysine (63.5)
Fig. 3
Fig. 3
The number of feasible elementary modes with respect to change in the stoichiometric value of NADP in the biomass definition
Fig. 4
Fig. 4
Value of optimal biomass yield with respect to change in the stoichiometric value of NADP in the biomass definition filled diamond. Solid line shows the trend line. Filled triangle and filled square shows maximum theoretical and experimental biomass yields, respectively
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