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Metabolic fluxes in riboflavin-producing Bacillus subtilis

Nature Biotechnology volume 15, pages 448–452 (1997)Cite this article

Abstract

The pentose phosphate pathway and the pyruvate shunt were identified as major pathways of glucose catabolism in a recombinant, riboflavin-producing Bacillus subtilis strain. Reactions connecting the tricarboxylic acid cycle and glycolysis, catalyzed by the malic enzyme and phosphoenolpyruvate carboxykinase, consume up to 23% of the metabolized glucose. These are examples of important fluxes that can be accessed explicitly using a novel analysis based on synergistic application of flux balancing and recently introduced techniques of fractional 13C-labeling and two-dimensional nuclear magnetic resonance spectroscopy. The overall flux distribution also suggests that B. subtilis metabolism has an unusually high capacity for the reoxidation of NADPH. Under the conditions investigated, riboflavin formation in B. subtilis is limited by the fluxes through the biosynthetic rather than the central carbon pathways, which suggests a focus for future metabolic engineering of this system.

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Author notes

  1. Thomas Szyperski: (e-mail: thom@mol.biol.ethz.ch)

Authors and Affiliations

  1. Institut für Biotechnologie and Institut für Molekularbiologie, ETH Zürich, CH-8093, Zurich, Switzerland

    Uwe Sauer, Vassily Hatzimanikatis & James E. Bailey

  2. Biophysik, ETH Zürich, CH-8093, Zurich, Switzerland

    Michel Hochuli, Thomas Szyperski & Kurt Wüthrich

Authors
  1. Uwe Sauer
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  2. Vassily Hatzimanikatis
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  3. James E. Bailey
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  4. Michel Hochuli
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  5. Thomas Szyperski
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  6. Kurt Wüthrich
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Sauer, U., Hatzimanikatis, V., Bailey, J. et al. Metabolic fluxes in riboflavin-producing Bacillus subtilis. Nat Biotechnol 15, 448–452 (1997). https://doi.org/10.1038/nbt0597-448

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