An important priority for many metabolic engineers is the production of a fast growing, easily controllable microbe that can turn methane - a strong greenhouse gas - into biofuel. A multi-team initiative funded by the Department of Energy's Advanced Research Projects Agency (of which I am a part) is pursuing this goal, and a recent paper has made a pretty substantial step forward. They've identified the genes needed to produce F430, a critical nickel-containing cofactor for the Mcr (methyl coenzyme M reductase) enzyme. F430 is where the catalytic magic of methane oxidation and production happens. If these five genes can be expressed along with the Mcr subunits and any accessory proteins needed to activate the enzyme itself, then methane's carbon - long regarded as a tough nut to crack - could become available for E. coli's central carbon metabolism.

Abstract below, full paper at Science is [here].

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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