Prokaryotic heme biosynthesis:Multiple pathways to a common essential product

Dailey, Harry A., Dailey, Tamara A., Gerdes, Svetlana, Jahn, Dieter, Jahn, Martina, O'Brian, Mark R. and Warren, Martin J. ORCID: (2017) Prokaryotic heme biosynthesis:Multiple pathways to a common essential product. Microbiology and Molecular Biology Reviews, 81 (1). ISSN 1092-2172

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The advent of heme during evolution allowed organisms possessing this compound to safely and efficiently carry out a variety of chemical reactions that otherwise were difficult or impossible. While it was long assumed that a single heme biosynthetic pathway existed in nature, over the past decade, it has become clear that there are three distinct pathways among prokaryotes, although all three pathways utilize a common initial core of three enzymes to produce the intermediate uroporphyrinogen III. The most ancient pathway and the only one found in the Archaea converts siroheme to protoheme via an oxygen-independent four-enzymestep process. Bacteria utilize the initial core pathway but then add one additional common step to produce coproporphyrinogen III. Following this step, Gram-positive organisms oxidize coproporphyrinogen III to coproporphyrin III, insert iron to make coproheme, and finally decarboxylate coproheme to protoheme, whereas Gramnegative bacteria first decarboxylate coproporphyrinogen III to protoporphyrinogen IX and then oxidize this to protoporphyrin IX prior to metal insertion to make protoheme. In order to adapt to oxygen-deficient conditions, two steps in the bacterial pathways have multiple forms to accommodate oxidative reactions in an anaerobic environment. The regulation of these pathways reflects the diversity of bacterial metabolism. This diversity, along with the late recognition that three pathways exist, has significantly slowed advances in this field such that no single organism's heme synthesis pathway regulation is currently completely characterized.

Item Type: Article
Additional Information: Funding Information: The research laboratory of H.A.D. is supported by NIH grant DK096051. D.J. and M.J. are supported by the Deutsche Forschungsgemeinschaft. M.R.O. is funded by NIH grant GM099667. M.J.W. is supported by grants from the Biotechnology and Biological Sciences Research Council. We acknowledge that we have no conflict of interest regarding the contents of the manuscript. Publisher Copyright: © 2017 American Society for Microbiology. All Rights Reserved.
Uncontrolled Keywords: biosynthetic pathways,heme,metabolic regulation,pathway evolution,tetrapyrroles,microbiology,molecular biology,infectious diseases,sdg 3 - good health and well-being ,/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 14:30
Last Modified: 24 Oct 2022 06:52
DOI: 10.1128/MMBR.00048-16

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