The Chlorite Dismutase (HemQ) from Staphylococcus aureus Has a Redox-sensitive Heme and Is Associated with the Small Colony Variant Phenotype

Gerdes

Proc. Natl. Acad. Sci. U.S.A.

et al. 2015

153

252

It has been generally accepted that biosynthesis of protoheme (heme) uses a common set of core metabolic intermediates that includes protoporphyrin. Herein, we show that the Actinobacteria and Firmicutes (high-GC and low-GC Gram-positive bacteria) are unable to synthesize protoporphyrin. Instead, they oxidize coproporphyrinogen to coproporphyrin, insert ferrous iron to make Fe-coproporphyrin (coproheme), and then decarboxylate coproheme to generate protoheme. This pathway is specified by three genes named hemY, hemH, and hemQ. The analysis of 982 representative prokaryotic genomes is consistent with this pathway being the most ancient heme synthesis pathway in the Eubacteria. Our results identifying a previously unknown branch of tetrapyrrole synthesis support a significant shift from current models for the evolution of bacterial heme and chlorophyll synthesis. Because some organisms that possess this coproporphyrin-dependent branch are major causes of human disease, HemQ is a novel pharmacological target of significant therapeutic relevance, particularly given high rates of antimicrobial resistance among these pathogens.

Section: Identification Of the Terminal Enzymes Of Gram-positive Hemesupporting

confidence: 82%

Section: Identification Of the Terminal Enzymes Of Gram-positive Hemesupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Section: Identification Of the Terminal Enzymes Of Gram-positive Hemementioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Noncanonical coproporphyrin-dependent bacterial heme biosynthesis pathway that does not use protoporphyrin

Gerdes

Proc. Natl. Acad. Sci. U.S.A.

et al. 2015

153

252

Encyclopedia of Inorganic and Bioinorganic Chemistry

Coproheme Decarboxylase

Hofbauer¹,

Furtmüller²

2021

Coproheme decarboxylases are essential enzymes within prokaryotic heme biosynthesis. These pentameric enzymes catalyze the ultimate reaction of the so‐called coproporphyrin‐dependent pathway, yielding the final product heme b by oxidative decarboxylation of two propionate groups of the substrate coproheme. The reaction occurs in a stepwise manner and transiently produces a three‐propionate intermediate during catalysis. In coproheme decarboxylases, the iron‐containing porphyrin substrate is the essential redox‐active molecule, which is required for the decarboxylation of the propionate groups and formation of the heme b vinyls. The reaction is initiated by an oxidant, most likely hydrogen peroxide, to lift the ferric iron of coproheme to the two‐electron‐deficient coproheme‐Compound I species. A catalytic tyrosine, in close proximity to the propionate to be cleaved, delivers an electron to form a neutral tyrosyl radical, which further attacks the β‐carbon of the propionate group and triggers the decarboxylation reaction, yielding a carbon dioxide molecule and a remaining vinyl group on the porphyrin. Structurally, coproheme decarboxylases are described by five subunits, which are arranged in a ring‐like manner to form the homopentameric enzyme. One subunit is built of two ferredoxin‐like folds, which are connected by a flexible linker. The C‐terminal domain is the catalytically relevant one, which is able to bind coproheme.

Chlorite dismutases – a heme enzyme family for use in bioremediation and generation of molecular oxygen

Hofbauer

Schaffner

Furtmüller

et al. 2014

Biotechnology Journal

104

Chlorite is a serious environmental concern, as rising concentrations of this harmful anthropogenic compound have been detected in groundwater, drinking water, and soil. Chlorite dismutases (Clds) are therefore important molecules in bioremediation as Clds catalyze the degradation of chlorite to chloride and molecular oxygen. Clds are heme b-containing oxidoreductases present in numerous bacterial and archaeal phyla. This review presents the phylogeny of functional Clds and Cld-like proteins, and demonstrates the close relationship of this novel enzyme family to the recently discovered dye-decolorizing peroxidases. The available X-ray structures, biophysical and enzymatic properties, as well as a proposed reaction mechanism, are presented and critically discussed. Open questions about structure-function relationships are addressed, including the nature of the catalytically relevant redox and reaction intermediates and the mechanism of inactivation of Clds during turnover. Based on analysis of currently available data, chlorite dismutase from “Candidatus Nitrospira defluvii” is suggested as a model Cld for future application in biotechnology and bioremediation. Additionally, Clds can be used in various applications as local generators of molecular oxygen, a reactivity already exploited by microbes that must perform aerobic metabolic pathways in the absence of molecular oxygen. For biotechnologists in the field of chemical engineering and bioremediation, this review provides the biochemical and biophysical background of the Cld enzyme family as well as critically assesses Cld's technological potential.