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Title: Post-translational thioamidation of methyl-coenzyme M reductase, a key enzyme in methanogenic and methanotrophic Archaea

Methyl-coenzyme M reductase (MCR), found in strictly anaerobic methanogenic and methanotrophic archaea, catalyzes the reversible production and consumption of the potent greenhouse gas methane. The α subunit of MCR (McrA) contains several unusual post-translational modifications, including a rare thioamidation of glycine. Based on the presumed function of homologous genes involved in the biosynthesis of thioviridamide, a thioamide-containing natural product, we hypothesized that the archaeal tfuA and ycaO genes would be responsible for post-translational installation of thioglycine into McrA. Mass spectrometric characterization of McrA from the methanogenic archaeon Methanosarcina acetivorans lacking tfuA and/or ycaO revealed the presence of glycine, rather than thioglycine, supporting this hypothesis. Phenotypic characterization of the ∆ycaO-tfuA mutant revealed a severe growth rate defect on substrates with low free energy yields and at elevated temperatures (39°C - 45°C). Our analyses support a role for thioglycine in stabilizing the protein secondary structure near the active site.
Authors:
ORCiD logo [1] ; ORCiD logo [2] ; ORCiD logo [3] ; ORCiD logo [4]
  1. Univ. of Illinois at Urbana-Champaign, IL (United States). Carl R. Woese Inst. for Genomic Biology
  2. Univ. of Illinois at Urbana-Champaign, IL (United States). Dept. of Chemistry
  3. Univ. of Illinois at Urbana-Champaign, IL (United States). Carl R. Woese Inst. for Genomic Biology and Dept. of Chemistry and Dept. of Microbiology
  4. Univ. of Illinois at Urbana-Champaign, IL (United States). Carl R. Woese Inst. for Genomic Biology and Dept. of Microbiology
Publication Date:
Grant/Contract Number:
FG02-02ER15296; GM097142
Type:
Published Article
Journal Name:
eLife
Additional Journal Information:
Journal Volume: 6; Journal ID: ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.
Research Org:
Univ. of Illinois at Urbana-Champaign, IL (United States)
Sponsoring Org:
USDOE; National Institutes of Health (NIH); Simons Foundation; Life Sciences Research Foundation (LSRF)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 54 ENVIRONMENTAL SCIENCES
OSTI Identifier:
1378144
Alternate Identifier(s):
OSTI ID: 1378147; OSTI ID: 1429098