Date of this Version
Lieber DJ, Catlett J, Madayiputhiya N, Nandakumar R, Lopez MM, et al. (2014) A Multienzyme Complex Channels Substrates and Electrons through Acetyl-CoA and Methane Biosynthesis Pathways in Methanosarcina. PLoS ONE 9(9): e107563. doi:10.1371/journal.pone.0107563
Multienzyme complexes catalyze important metabolic reactions in many organisms, but little is known about the complexes involved in biological methane production (methanogenesis). A crosslinking-mass spectrometry (XL-MS) strategy was employed to identify proteins associated with coenzyme M-coenzyme B heterodisulfide reductase (Hdr), an essential enzyme in all methane-producing archaea (methanogens). In Methanosarcina acetivorans, Hdr forms a multienzyme complex with acetyl-CoA decarbonylase synthase (ACDS), and F420-dependent methylene-H4MPT reductase (Mer). ACDS is essential for production of acetyl-CoA during growth on methanol, or for methanogenesis from acetate, whereas Mer is essential for methanogenesis from all substrates. Existence of a Hdr:ACDS:Mer complex is consistent with growth phenotypes of ACDS and Mer mutant strains in which the complex samples the redox status of electron carriers and directs carbon flux to acetyl-CoA or methanogenesis. We propose the Hdr:ACDS:Mer complex comprises a special class of multienzyme redox complex which functions as a ‘‘biological router’’ that physically links methanogenesis and acetyl-CoA biosynthesis pathways.