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From genome to cellular phenotype—a role for metabolic flux analysis?

Nature Biotechnology volume 18, pages 267–268 (2000)Cite this article

More than 20 genomes have been completely sequenced, and the first draft of the complete human genome is expected this year1. This barrage of information should eventually lead to a better understanding of cellular physiology, which in turn may then be exploited to advance human health, agricultural production, and industrial fermentation. If the physiology of the organism under study is relatively well understood, such as for Escherichia coli or yeast, the compilation of this sequence data to reconstruct metabolic pathways may seem a reasonable challenge. However, if there is only limited biochemical information available, such as for Treponema pallidum (the causative agent of syphilis), a partial list of putative enzymes is unlikely to allow metabolic networks and cellular phenotypes to be established. Realistically, a list of genes alone is not enough to understand the pathophysiology or manipulate the metabolism of T. pallidum. Thus, a robust method of converting a list of putative enzymes into a set of metabolic pathways could be a powerful bioinformatic tool. In this issue, Schuster et al.2 discuss a means of defining pathways rigorously and show how to express their constitutive activities as the sum of “elementary flux modes”, each of which represents a minimal sequence of steps that can in principle operate independantly of any others.

Elementary flux modes can be determined mathematically from the list of reactions in the system, without any kinetic information. Any conceivable set of fluxes becomes a weighted sum of the elementary modes. Glycolysis and the pentose phosphate pathway, for example, can be regarded in the simplest case as the sum of seven elementary modes. This may seem very abstract and only of interest to the theoretical biologist, without any practical implications for biotechnology. Indeed, why should a biotechnologist care whether metabolic pathways are rigorously defined or not?

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Figure 1: The necessary steps to convert a genome sequence into a phenotypic description include not only the early stages of identifying the genes, but also later ones that have received less attention: assembling the enzyme-catalyzed reactions into a metabolic map, determining what kinds of metabolic activity are stoichiometrically possible, and finally, determining which of these are kinetically possible.

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Authors and Affiliations

  1. director of research in the laboratory Bioénergétique et Ingéniérie des Protéines of the Institut Fédératif Biologie Structurale et Microbiologie, CNRS, Marseilles, France

    Athel Cornish-Bowden

  2. research associate in the laboratory Bioénergétique et Ingéniérie des Protéines of the Institut Fédératif Biologie Structurale et Microbiologie, CNRS, Marseilles, France

    María Luz Cárdenas

Authors
  1. Athel Cornish-Bowden
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  2. María Luz Cárdenas
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Cornish-Bowden, A., Luz Cárdenas, M. From genome to cellular phenotype—a role for metabolic flux analysis? . Nat Biotechnol 18, 267–268 (2000). https://doi.org/10.1038/73696

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