title: Prokaryotic Heme Biosynthesis: Multiple Pathways to a Common Essential Product.
abstract: 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-enzyme-step 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 Gram-negative 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.
authors.affiliation: Department of Microbiology, Department of Biochemistry and Molecular Biology, and Biomedical and Health Sciences Institute, University of Georgia, Athens, Georgia, USA hdailey@uga.edu.
authors.forename: Harry A
authors.initials: HA
authors.lastname: Dailey
authors.affiliation: Department of Microbiology, Department of Biochemistry and Molecular Biology, and Biomedical and Health Sciences Institute, University of Georgia, Athens, Georgia, USA.
authors.forename: Tamara A
authors.initials: TA
authors.lastname: Dailey
authors.affiliation: Fellowship for Interpretation of Genomes, Burr Ridge, Illinois, USA.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Gerdes
authors.affiliation: Braunschweig Integrated Centre of Systems Biology (BRICS), Technische Universitaet Braunschweig, Braunschweig, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Jahn
authors.affiliation: Institute of Microbiology, Technische Universitaet Braunschweig, Braunschweig, Germany.
authors.forename: Martina
authors.identifier: 0000-0002-8345-6550
authors.initials: M
authors.lastname: Jahn
authors.affiliation: Department of Biochemistry, University at Buffalo, The State University of New York, Buffalo, New York, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: O'Brian
authors.affiliation: Department of Biosciences, University of Kent, Canterbury, Kent, United Kingdom.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Warren
mesh_terms: D000622:Aminolevulinic Acid / Q000378:metabolism; D001105:Archaea / Q000378:metabolism*; D001419:Bacteria / Q000378:metabolism*; D003304:Coproporphyrinogen Oxidase / Q000378:metabolism; D003306:Coproporphyrins / Q000378:metabolism; D006418:Heme / Q000031:analogs & derivatives* / Q000096:biosynthesis; D007501:Iron / Q000737:chemistry*; D011524:Protoporphyrins / Q000096:biosynthesis / Q000378:metabolism; D045725:Tetrapyrroles / Q000096:biosynthesis*; D014575:Uroporphyrinogen Decarboxylase / Q000378:metabolism
chemical_list: D003306:Coproporphyrins; D011524:Protoporphyrins; D045725:Tetrapyrroles; C026971:coproporphyrin III; D006418:Heme; C009272:siroheme; C029400:heme d1; C011539:protoporphyrinogen; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; D007501:Iron; D003304:Coproporphyrinogen Oxidase; D014575:Uroporphyrinogen Decarboxylase
keywords: biosynthetic pathways; heme; metabolic regulation; pathway evolution; tetrapyrroles