ChuW - the CFM for this family - has been demonstrated to form part of an oxygen-independent heme-degradation pathway. Specifically, ChuW facilitates the liberation of iron and produces a tetrapyrrole product termed "anaerobilin" by LaMattina et al.
Dailey HA, Gerdes S, Dailey TA, Burch JS, Phillips JD
Noncanonical coproporphyrin-dependent bacterial heme biosynthesis pathway that does not use protoporphyrin
▸ Abstract
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.
Proc Natl Acad Sci U S A
2015;112(7):2210-2215
| PubMed ID:
25646457
LaMattina JW, Nix DB, Lanzilotta WN
Radical new paradigm for heme degradation in Escherichia coli O157:H7
▸ Abstract
All of the heme-degrading enzymes that have been characterized to date require molecular oxygen as a cosubstrate. Escherichia coli O157:H7 has been shown to express heme uptake and transport proteins, as well as use heme as an iron source. This enteric pathogen colonizes the anaerobic space of the lower intestine in mammals, yet no mechanism for anaerobic heme degradation has been reported. Herein we provide evidence for an oxygen-independent heme-degradation pathway. Specifically, we demonstrate that ChuW is a radical S-adenosylmethionine methyltransferase that catalyzes a radical-mediated mechanism facilitating iron liberation and the production of the tetrapyrrole product we termed "anaerobilin." We further demonstrate that anaerobilin can be used as a substrate by ChuY, an enzyme that is coexpressed with ChuW in vivo along with the heme uptake machinery. Our findings are discussed in terms of the competitive advantage this system provides for enteric bacteria, particularly those that inhabit an anaerobic niche in the intestines.
Proc Natl Acad Sci U S A
2016;113(43):12138-12143
| PubMed ID:
27791000
