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Systems biology

Metabolite turns master regulator

Nature volume 500, pages 283–284 (2013)Cite this article

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The phenomenon of catabolite repression enables microorganisms to use their favourite carbon source first. New work reveals α-ketoacids as key effectors of this process, with their levels regulating gene expression. See Article p.301

Nutrients in the environment are a primary determinant of microbial physiology. When preferred nutrients are abundant, microbes grow fast. When they are scarce, growth slows down. This change in growth rate is accompanied by a change in cellular composition, with fast-growing cells being loaded with ribosomes (which are needed for rapid protein production), and slower-growing cells containing more metabolic enzymes for nutrient assimilation (catabolism)1,2. In this issue, You et al. (page 301)3 identify a striking linear relationship between the total protein composition (the proteome) of a cell and its growth rate, which extends beyond ribosomes to metabolic enzymesFootnote 1. They further demonstrate how such a relationship can arise, in part, from a new regulatory connection, in which a particular class of carbon catabolite called α-ketoacids, which form the carbon skeletons of amino acids, serves as a master transcriptional regulator by inhibiting the production of cyclic AMP — the primary inducer of carbon-catabolic genes.

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Figure 1: Regulation of cAMP levels by carbon and nitrogen availability.

Notes

  1. *This article and the paper under discussion3 were published online on 7 August 2013.

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Authors and Affiliations

  1. Joshua D. Rabinowitz is in the Department of Chemistry and at the Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA.,

    Joshua D. Rabinowitz

  2. Thomas J. Silhavy is in the Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.,

    Thomas J. Silhavy

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  1. Joshua D. Rabinowitz
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  2. Thomas J. Silhavy
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Correspondence to Joshua D. Rabinowitz.

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Rabinowitz, J., Silhavy, T. Metabolite turns master regulator. Nature 500, 283–284 (2013). https://doi.org/10.1038/nature12544

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