Staphylococcus aureus haem biosynthesis: characterisation of the enzymes involved in final steps of the pathway. Issue 3 (26th May 2015)

• Record Type: Journal Article
• Authors: 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.; Saraiva, Lígia M.
• Is Part Of: Molecular microbiology. Volume 97:Issue 3(2015)
• Page Start: 472
• Page End: 487
• Publication Date: 2015-05-26
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.13041
• Languages: English
• ISSNs: 0950-382X

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>Haem is a life supporting molecule that is ubiquitous in all major kingdoms. In <italic>S</italic><italic>taphylococcus aureus</italic>, 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 <italic>S</italic><italic>. aureus</italic> 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 <italic>S</italic><italic>. aureus</italic>. 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.</p> </abstract>