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The biosynthetic pathway of coenzyme F430 in methanogenic and methanotrophic archaea

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Science  21 Oct 2016:
Vol. 354, Issue 6310, pp. 339-342
DOI: 10.1126/science.aag2947

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Enzymes for making (or breaking) methane

The last enzymatic step of microbial methanogenesis, and the first step of microbial methane oxidation, relies on the nickel-containing tetrapyrrole coenzyme F430. The successful metabolic engineering of any organism to enzymatically consume methane thus also needs the appropriate machinery to synthesize this compound. Using comparative genomics, Zheng et al. identified several candidate genes responsible for coenzyme F430 biosynthesis. Cloning and expression of all the subsequent proteins in Escherichia coli confirmed the complete in vitro conversion of sirohydrochlorin into mature F430.

Science, this issue p. 339

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.

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