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Biochem J. 2018 Jun 6;475(11):1909-1937. doi: 10.1042/BCJ20180043.

Protein CoAlation and antioxidant function of coenzyme A in prokaryotic cells.

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Department of Structural and Molecular Biology, University College London, London WC1E 6BT, U.K.
The Francis Crick Institute, London NW1 1AT, U.K.
Department of Biochemical Engineering, University College London, London WC1E 6BT, U.K.
Department of Chemistry, University College London, London WC1H 0AJ, U.K.
Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv 03680, Ukraine.
Biological Mass Spectrometry and Proteomics Cell Biology, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, U.K.
Department of Structural and Molecular Biology, University College London, London WC1E 6BT, U.K.


In all living organisms, coenzyme A (CoA) is an essential cofactor with a unique design allowing it to function as an acyl group carrier and a carbonyl-activating group in diverse biochemical reactions. It is synthesized in a highly conserved process in prokaryotes and eukaryotes that requires pantothenic acid (vitamin B5), cysteine and ATP. CoA and its thioester derivatives are involved in major metabolic pathways, allosteric interactions and the regulation of gene expression. A novel unconventional function of CoA in redox regulation has been recently discovered in mammalian cells and termed protein CoAlation. Here, we report for the first time that protein CoAlation occurs at a background level in exponentially growing bacteria and is strongly induced in response to oxidizing agents and metabolic stress. Over 12% of Staphylococcus aureus gene products were shown to be CoAlated in response to diamide-induced stress. In vitro CoAlation of S. aureus glyceraldehyde-3-phosphate dehydrogenase was found to inhibit its enzymatic activity and to protect the catalytic cysteine 151 from overoxidation by hydrogen peroxide. These findings suggest that in exponentially growing bacteria, CoA functions to generate metabolically active thioesters, while it also has the potential to act as a low-molecular-weight antioxidant in response to oxidative and metabolic stress.


Gram-negative and -positive bacteria; coenzyme A; post-translational modification; redox signaling

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