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Metabolite damage and its repair or pre-emption

Nature Chemical Biology volume 9, pages 72–80 (2013)Cite this article

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Abstract

It is increasingly evident that metabolites suffer various kinds of damage, that such damage happens in all organisms and that cells have dedicated systems for damage repair and containment. First, chemical biology is demonstrating that diverse metabolites are damaged by side reactions of 'promiscuous' enzymes or by spontaneous chemical reactions, that the products are useless or toxic and that the unchecked buildup of these products can be devastating. Second, genetic and genomic evidence from prokaryotes and eukaryotes is implicating a network of new, conserved enzymes that repair damaged metabolites or somehow pre-empt damage. Metabolite (that is, small-molecule) repair is analogous to macromolecule (DNA and protein) repair and seems from comparative genomic evidence to be equally widespread. Comparative genomics also implies that metabolite repair could be the function of many conserved protein families lacking known activities. How—and how well—cells deal with metabolite damage affects fields ranging from medical genetics to metabolic engineering.

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Figure 1: Damage-control systems in biology.
Figure 2: Coenzyme damage and repair reactions.
Figure 3: Pathway intermediate damage and repair reactions.
Figure 4: Damage pre-emption mechanisms.
Figure 5: Clustering patterns of some bacterial metabolite repair genes.

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Acknowledgements

The authors' research on metabolite damage control is supported by the US National Science Foundation (award no. MCB-1153413 to A.D.H.), the Fonds National de la Recherche Scientifique (to E.V.S. and C.L.L.), the Walloon Region (WELBIO to E.V.S.) and the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement 276814 (to C.L.L.). We thank M. Stitt, J.R. Roth and T.P. Begley for insightful discussions and V. de Crécy-Lagard, O. Fiehn and C.S. Henry for critically reading this article.

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  1. Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg

    Carole L Linster

  2. Walloon Excellence in Lifesciences and Biotechnology (WELBIO), de Duve Institute, Catholic University of Louvain, Brussels, Belgium

    Emile Van Schaftingen

  3. Horticultural Sciences Department, University of Florida, Gainesville, Florida, USA

    Andrew D Hanson

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Linster, C., Van Schaftingen, E. & Hanson, A. Metabolite damage and its repair or pre-emption. Nat Chem Biol 9, 72–80 (2013). https://doi.org/10.1038/nchembio.1141

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