title: The biosynthetic pathway of coenzyme F430 in methanogenic and methanotrophic archaea.
abstract: Methyl-coenzyme M reductase (MCR) is the key enzyme of methanogenesis and anaerobic methane oxidation. The activity of MCR is dependent on the unique nickel-containing tetrapyrrole known as coenzyme F430. We used comparative genomics to identify the coenzyme F430 biosynthesis (cfb) genes and characterized the encoded enzymes from Methanosarcina acetivorans C2A. The pathway involves nickelochelation by a nickel-specific chelatase, followed by amidation to form Ni-sirohydrochlorin a,c-diamide. Next, a primitive homolog of nitrogenase mediates a six-electron reduction and γ-lactamization reaction before a Mur ligase homolog forms the six-membered carbocyclic ring in the final step of the pathway. These data show that coenzyme F430 can be synthesized from sirohydrochlorin using Cfb enzymes produced heterologously in a nonmethanogen host and identify several targets for inhibitors of biological methane formation.
authors.affiliation: Department of Chemistry and Biochemistry, Auburn University, Auburn, AL 36849, USA.
authors.forename: Kaiyuan
authors.initials: K
authors.lastname: Zheng
authors.affiliation: Department of Chemistry and Biochemistry, Auburn University, Auburn, AL 36849, USA.
authors.forename: Phong D
authors.initials: PD
authors.lastname: Ngo
authors.affiliation: Department of Chemistry and Biochemistry, Auburn University, Auburn, AL 36849, USA.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Owens
authors.affiliation: Department of Chemistry and Biochemistry, Auburn University, Auburn, AL 36849, USA.
authors.forename: Xue-Peng
authors.initials: XP
authors.lastname: Yang
authors.affiliation: Department of Chemistry and Biochemistry, Auburn University, Auburn, AL 36849, USA. som@auburn.edu.
authors.forename: Steven O
authors.initials: SO
authors.lastname: Mansoorabadi
mesh_terms: D000577:Amides / Q000378:metabolism; D019843:Archaeal Proteins / Q000235:genetics / Q000378:metabolism*; D053898:Biosynthetic Pathways; D019766:Genes, Archaeal; D056426:Genetic Loci; D023281:Genomics; D008665:Metalloporphyrins / Q000235:genetics / Q000378:metabolism*; D008697:Methane / Q000378:metabolism*; D017020:Methanosarcina / Q000201:enzymology* / Q000235:genetics; D009532:Nickel / Q000378:metabolism; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D014578:Uroporphyrins / Q000378:metabolism*
chemical_list: D000577:Amides; D019843:Archaeal Proteins; D008665:Metalloporphyrins; D014578:Uroporphyrins; C014188:sirohydrochlorin; C023540:factor F430; D009532:Nickel; D010088:Oxidoreductases; C021572:methyl coenzyme M reductase; D008697:Methane