Staphylococcus aureus haem biosynthesis:Characterisation of the enzymes involved in final steps of the pathway

Lobo, Susana A.L., Scott, Alan, Videira, Marco A.M., Winpenny, David, Gardner, Mark, Palmer, Mike J., Schroeder, Susanne, Lawrence, Andrew D., Parkinson, Tanya, Warren, Martin J. ORCID: https://orcid.org/0000-0002-6028-6456 and Saraiva, Lígia M. (2015) Staphylococcus aureus haem biosynthesis:Characterisation of the enzymes involved in final steps of the pathway. Molecular Microbiology, 97 (3). pp. 472-487. ISSN 0950-382X

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Abstract

Haem is a life supporting molecule that is ubiquitous in all major kingdoms. In Staphylococcus aureus, the importance of haem is highlighted by the presence of systems both for the exogenous acquisition and endogenous synthesis of this prosthetic group. In this work, we show that in S.aureus the formation of haem involves the conversion of coproporphyrinogen III into coproporphyrin III by coproporphyrin synthase HemY, insertion of iron into coproporphyrin III via ferrochelatase HemH, and oxidative decarboxylation of Fe-coproporphyrin III into protohaem IX by Fe-coproporphyrin oxidase/dehydrogenase HemQ. Together, this route represents a transitional pathway between the classic pathway and the more recently acknowledged alternative biosynthesis machinery. The role of the haem biosynthetic pathway in the survival of the bacterium was investigated by testing for inhibitors of HemY. Analogues of acifluorfen are shown to inhibit the flavin-containing HemY, highlighting this protein as a suitable target for the development of drugs against S.aureus. Moreover, the presence of a transitional pathway for haem biosynthesis within many Gram positive pathogenic bacteria suggests that this route has the potential not only for the design of antimicrobials but also for the selective discrimination between bacteria operating different routes to the biosynthesis of haem.

Item Type: Article
Additional Information: Publisher Copyright: © 2015 John Wiley & Sons Ltd.
Uncontrolled Keywords: microbiology,molecular biology ,/dk/atira/pure/subjectarea/asjc/2400/2404
Faculty \ School: Faculty of Science
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Depositing User: LivePure Connector
Date Deposited: 20 Sep 2022 14:31
Last Modified: 27 Sep 2022 08:36
URI: https://ueaeprints.uea.ac.uk/id/eprint/88491
DOI: 10.1111/mmi.13041

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