title: 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.
authors: Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602; Center for Metalloenzyme Studies, University of Georgia, Athens, GA 30602.
authors: Joseph W
authors: JW
authors: LaMattina
authors: Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602; Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602.
authors: David B
authors: DB
authors: Nix
authors: Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602; Center for Metalloenzyme Studies, University of Georgia, Athens, GA 30602; wlanzilo@bmb.uga.edu.
authors: William Nicholas
authors: WN
authors: Lanzilotta
mesh_terms: D000693:Anaerobiosis; D001692:Biological Transport; D019453:Escherichia coli O157 / Q000201:enzymology* / Q000235:genetics; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D005418:Flavodoxin / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006418:Heme / Q000378:metabolism*; D006420:Hemeproteins / Q000235:genetics / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics / Q000378:metabolism*; D011497:Protein O-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D045725:Tetrapyrroles / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C541919:ChuX protein, E coli; D029968:Escherichia coli Proteins; D005418:Flavodoxin; D005609:Free Radicals; D006420:Hemeproteins; D045725:Tetrapyrroles; C000618860:anaerobilin; D006418:Heme; D007501:Iron; C000618859:ChuY protein, E coli; D044925:Oxidoreductases Acting on CH-CH Group Donors; D011497:Protein O-Methyltransferase
keywords: anaerobic; heme; intestinal microbiome; pathogen; radical SAM