Elucidation of the biosynthesis of the methane catalyst coenzyme F430

Methane biogenesis in methanogens is mediated by methyl-coenzyme M reductase, an enzyme that is also responsible for the utilization of methane through anaerobic methane oxidation. The enzyme uses an ancillary factor called coenzyme F 430 , a nickel-containing modified tetrapyrrole that promotes catalysis through a methyl radical/Ni( ii )-thiolate intermediate. However, it is unclear how coenzyme F 430 is synthesized from the common primogenitor uroporphyrinogen iii , incorporating 11 steric centres into the macrocycle, although the pathway must involve chelation, amidation, macrocyclic ring reduction, lactamization and carbocyclic ring formation. Here we identify the proteins that catalyse the biosynthesis of coenzyme F 430 from sirohydrochlorin, termed CfbA–CfbE, and demonstrate their activity. The research completes our understanding of how the repertoire of tetrapyrrole-based pigments are constructed, permitting the development of recombinant systems to use these metalloprosthetic groups more widely. The enzymes and pathway involved in the biosynthesis of coenzyme F 430 are identified, completing our understanding of how members of the cyclic modified tetrapyrrole family are constructed. Methane catalyst's molecular make-up Methanogenesis, the biosynthesis of methane by microorganisms, produces around a billion tons of methane gas per year—a significant contribution to global warming. Coenzyme F430 is a nickel-containing modified tetrapyrrole that catalyses the generation of methane, but how it forms is not fully understood. In this work, Martin Warren and co-workers identify the genes responsible for F430 biosynthesis and demonstrate the activities of each of the key enzymes involved. The authors show how the molecular framework that houses nickel is assembled to optimize methanogenesis. Clarifying the pathway to this coenzyme also completes our understanding of how other members of the modified tetrapyrrole family are constructed.