Metabolite damage and its repair or pre-emption

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• Prof. Andrew Hanson, Horticultural sciences department (University of Florida)
• Monday 05 October 2015, 14:00-15:30
• Department of Biochemistry, Hopkins Building, Seminar Room 1.

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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. Firstly, 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. Secondly, genetic and genomic evidence from pro- and eukaryotes is implicating a network of novel, conserved enzymes that repair damaged metabolites or somehow pre-empt damage. Metabolite (i.e. small molecule) repair is analogous to macromolecule (DNA and protein) repair and appears 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 impacts fields ranging from medical genetics to metabolic engineering and synthetic biology.

Linster, C.L., Van Schaftingen, E., and Hanson, A.D. (2013). Metabolite damage and its repair or pre-emption. Nat. Chem. Biol. 9: 72–80.

Van Schaftingen, E., Rzem, R., Marbaix, A., Collard, F., Veiga-da-Cunha, M., and Linster, C.L. (2013). Metabolite proofreading, a neglected aspect of intermediary metabolism. J. Inherit. Metab. Dis. 36: 427–434.

Danchin, A., and Sekowska, A. (2014) The logic of metabolism and its fuzzy consequences. Environ. Microbiol. 16: 19–28. Gladyshev, V.N. (2012). On the cause of aging and control of lifespan: heterogeneity leads to inevitable damage accumulation, causing aging; control of damage composition and rate of accumulation define lifespan. Bioessays 34: 925–929.

This talk is part of the Seminars at the Department of Biochemistry series.

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