title: A multienzyme complex channels substrates and electrons through acetyl-CoA and methane biosynthesis pathways in Methanosarcina.
abstract: 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.
authors.affiliation: Department of Biochemistry and Redox Biology Center, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.
authors.forename: Dillon J
authors.initials: DJ
authors.lastname: Lieber
authors.affiliation: Department of Biochemistry and Redox Biology Center, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Catlett
authors.affiliation: Redox Biology Center Metabolomics Core Facility, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.
authors.forename: Nandu
authors.initials: N
authors.lastname: Madayiputhiya
authors.affiliation: Redox Biology Center Metabolomics Core Facility, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.
authors.forename: Renu
authors.initials: R
authors.lastname: Nandakumar
authors.affiliation: Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
authors.forename: Madeline M
authors.initials: MM
authors.lastname: Lopez
authors.affiliation: Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
authors.forename: William W
authors.initials: WW
authors.lastname: Metcalf
authors.affiliation: Department of Biochemistry and Redox Biology Center, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Buan
mesh_terms: D000085:Acetates / Q000378:metabolism; D000105:Acetyl Coenzyme A / Q000235:genetics / Q000378:metabolism; D000445:Aldehyde Oxidoreductases / Q000235:genetics / Q000378:metabolism; D002384:Catalysis; D008697:Methane / Q000096:biosynthesis; D017020:Methanosarcina / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism
chemical_list: D000085:Acetates; D009097:Multienzyme Complexes; D000105:Acetyl Coenzyme A; D010088:Oxidoreductases; C087171:heterodisulfide reductase; D000445:Aldehyde Oxidoreductases; C019823:carbon monoxide dehydrogenase; D008697:Methane