Biochemistry, Department of


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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


Copyright © 2014 Dillon J. Lieber, Jennifer Catlett, Nandu Madayiputhiya, Renu Nandakumar, Madeline M. Lopez, William W. Metcalf, Nicole R. Buan. This is an open-access article distributed under the terms of the Creative Commons Attribution License


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.