Approaches for completing metabolic networks through metabolite damage and repair discovery

Corey M Griffith; Adhish S Walvekar; Carole L Linster

doi:10.1016/j.coisb.2021.100379

Approaches for completing metabolic networks through metabolite damage and repair discovery

Curr Opin Syst Biol. 2021 Dec:28:None. doi: 10.1016/j.coisb.2021.100379.

Authors

Corey M Griffith¹, Adhish S Walvekar¹, Carole L Linster¹

Affiliation

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

Abstract

Metabolites are prone to damage, either via enzymatic side reactions, which collectively form the underground metabolism, or via spontaneous chemical reactions. The resulting non-canonical metabolites that can be toxic, are mended by dedicated "metabolite repair enzymes." Deficiencies in the latter can cause severe disease in humans, whereas inclusion of repair enzymes in metabolically engineered systems can improve the production yield of value-added chemicals. The metabolite damage and repair loops are typically not yet included in metabolic reconstructions and it is likely that many remain to be discovered. Here, we review strategies and associated challenges for unveiling non-canonical metabolites and metabolite repair enzymes, including systematic approaches based on high-resolution mass spectrometry, metabolome-wide side-activity prediction, as well as high-throughput substrate and phenotypic screens.

Keywords: Metabolite repair enzymes; Non-canonical metabolites; Underground metabolism; Untargeted metabolomics.

Publication types

Review