The biosynthesis and utilization of CoA (coenzyme A), the ubiquitous and essential acyl carrier in all organisms, have long been regarded as excellent targets for the development of new antimicrobial drugs. Moreover, bioinformatics and biochemical studies have highlighted significant differences between several of the bacterial enzyme targets and their human counterparts, indicating that selective inhibition of the former should be possible. Over the past decade, a large amount of structural and mechanistic data has been gathered on CoA metabolism and the CoA biosynthetic enzymes, and this has facilitated the discovery and development of several promising candidate antimicrobial agents. These compounds include both target-specific inhibitors, as well as CoA antimetabolite precursors that can reduce CoA levels and interfere with processes that are dependent on this cofactor. In the present mini-review we provide an overview of the most recent of these studies that, taken together, have also provided chemical validation of CoA biosynthesis and utilization as viable targets for antimicrobial drug development.
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Conference Article|
August 11 2014
Recent advances in targeting coenzyme A biosynthesis and utilization for antimicrobial drug development
Wessel J.A. Moolman;
Wessel J.A. Moolman
*Department of Biochemistry, Stellenbosch University, Stellenbosch, 7600, South Africa
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Marianne de Villiers;
Marianne de Villiers
*Department of Biochemistry, Stellenbosch University, Stellenbosch, 7600, South Africa
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Erick Strauss
Erick Strauss
1
*Department of Biochemistry, Stellenbosch University, Stellenbosch, 7600, South Africa
1To whom correspondence should be addressed (emailestrauss@sun.ac.za).
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Publisher: Portland Press Ltd
Received:
May 06 2014
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2014 Biochemical Society
2014
Biochem Soc Trans (2014) 42 (4): 1080–1086.
Article history
Received:
May 06 2014
Citation
Wessel J.A. Moolman, Marianne de Villiers, Erick Strauss; Recent advances in targeting coenzyme A biosynthesis and utilization for antimicrobial drug development. Biochem Soc Trans 1 August 2014; 42 (4): 1080–1086. doi: https://doi.org/10.1042/BST20140131
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