Thiaminedependent Decarboxylation Reactions in Methanogenic Coenzyme M Biosynthesis

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Thiamine-dependent Decarboxylation Reactions in
Methanogenic Coenzyme M Biosynthesis
David E. Graham, The University of Texas at
Austin Chemistry and Biochemistry Department.
Methanogens produce more than 400 Tg of methane
each year, corresponding to 80 of global methane
production from all sources. This methane is a
valuable energy source, as well as a greenhouse
gas. To develop new ways of controlling
methanogen- esis, we are elucidating the
biosynthetic pathways for Coenzyme M (CoM
2-mercaptoethane-sulfonate). CoM is the terminal
methyl carrier in all methanogens, so treatments
that block the biosynthesis of CoM or CoB could
be selective inhibitors of methanogenesis.
ESI-MS analysis of reaction products identified
cysteate in the reaction mixture with cysteate
synthase.
We have identified a new enzyme in the
microorganism Methanosarcina acetivorans that
allows this microbe to make CoM by a different
pathway from most methanogens. In this scheme,
cysteate synthase catalyzes the elimination of
phosphate from phosphoserine, and the resulting
dehydroalanine is sulfonated to form L-cysteate.
Transamination produces sulfopyruvate.
Sulfopyruvate decarboxylase (SPyDC) is a
thiamine-dependent enzyme that catalyzes the
penultimate step in CoM biosynthesis. We
developed a new expression system and analytical
techniques to study this oxygen-sensitive protein
and identify new inhibitors.