SummaryMethane biogenesis in methanogens is mediated by methyl-coenzyme M reductase, an enzyme that is also responsible for the utilisation of methane through anaerobic methane oxidation. The enzyme employs an ancillary factor called coenzyme F430, a nickel-containing modified tetrapyrrole that promotes catalysis through a novel methyl radical/Ni(II)-thiolate intermediate. However, the biosynthesis of coenzyme F430 from the common primogenitor uroporphyrinoge III, incorporating 11 steric centres into the macrocycle, has remained poorly understood although the pathway must involve chelation, amidation, macrocyclic ring reduction, lactamisation and carbocyclic ring formation. We have now identified the proteins that catalyse coenzyme F430 biosynthesis from sirohydrochlorin, termed CfbA-E, and shown their activity. The research completes our understanding of how nature is able to construct its repertoire of tetrapyrrole-based life pigments, permitting the development of recombinant systems to utilise these metalloprosthetic groups more widely.

In this Article, we omitted to cite a relevant paper 1 on coenzyme F 430 biosynthesis, which identified the genes that encode the enzymes required for the transformation of sirohydrochlorin into coenzyme F 430 and demonstrated their efficacy. Our study has confirmed these findings and also provided more detailed structural characterization of the pathway intermediates. We also showed that part of the pathway is operative in Escherichia coli, characterized the reductase system by electron paramagnetic resonance (EPR) and demonstrated that the formation of ring E is a chemical rather than biochemical reaction. We were unaware of this paper, which was published while our Article was under review.In addition, the genome annotations for the coenzyme F 430 biosynthesis (cfb) genes in the NCBI database have now been updated to reflect the naming conventions of ref. 1. In brief, the gene names of cfbD and cfbC have been swapped, as have those of the cfbB and cfbE genes. We thank S. Mansoorabadi for bringing the gene nomenclature issue to our attention. The original Article has not been corrected online.