The Pathway for Coenzyme M Biosynthesis in Bacteria

Hsin-Hua Wu, Michael Pun, Courtney Wise, Bennett Streit, Florence Mus, Anna Berim, William Kincannon, Abdullah Islam, Sarah Partovi, David Gang, Jennifer DuBois, Carolyn Lubner, Clifford Berkman, B. Markus Lange, John Peters

Research output: Contribution to journalArticlepeer-review

4 Scopus Citations


Mercaptoethane sulfonate or coenzyme M (CoM) is the smallest known organic cofactor and is most commonly associated with the methane-forming step in all methanogenic archaea but is also associated with the anaerobic oxidation of methane to CO2 in anaerobic methanotrophic archaea and the oxidation of short-chain alkanes in Syntrophoarchaeum species. It has also been found in a small number of bacteria capable of the metabolism of small organics. Although many of the steps for CoM biosynthesis in methanogenic archaea have been elucidated, a complete pathway for the biosynthesis of CoM in archaea or bacteria has not been reported. Here, we present the complete CoM biosynthesis pathway in bacteria, revealing distinct chemical steps relative to CoM biosynthesis in methanogenic archaea. The existence of different pathways represents a profound instance of convergent evolution. The five-step pathway involves the addition of sulfite, the elimination of phosphate, decarboxylation, thiolation, and the reduction to affect the sequential conversion of phosphoenolpyruvate to CoM. The salient features of the pathway demonstrate reactivities for members of large aspartase/fumarase and pyridoxal 50-phosphate–dependent enzyme families.

Original languageAmerican English
Article numbere2207190119
Number of pages7
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number36
StatePublished - 6 Sep 2022

Bibliographical note

Publisher Copyright:
Copyright © 2022 the Author(s).

NREL Publication Number

  • NREL/JA-2700-83674


  • aspartase/fumarase superfamily
  • CoM biosynthesis
  • PLP-dependent cysteine desulfhydrase
  • sulfonate
  • Xanthobacter autotrophicus


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