||Krishnamoorthy K, Begley TP.
||Protein thiocarboxylate-dependent methionine biosynthesis in Wolinella
||J Am Chem Soc.
||Thiocarboxylated proteins are important intermediates in a variety of
biochemical sulfide transfer reactions.
Here we identify a protein thiocarboxylate-dependent methionine biosynthetic
pathway in Wolinella succinogenes.
In this pathway, the carboxy terminal alanine of a novel sulfur transfer
protein, HcyS-Ala, is removed in a reaction catalyzed by a metalloprotease,
HcyD. HcyF, an ATP-utilizing enzyme, catalyzes the adenylation of HcyS.
HcyS acyl-adenylate then undergoes nucleophilic substitution by bisulfide
produced by Sir to give the HcyS thiocarboxylate.
This adds to O-acetylhomoserine to give HcyS-homocysteine in a PLP-dependent
reaction catalyzed by MetY. HcyD-mediated hydrolysis liberates homocysteine.
A final methylation completes the biosynthesis. The biosynthetic gene cluster
also encodes the enzymes involved in the conversion of sulfate to sulfide
suggesting that sulfate is the sulfur source for protein thiocarboxylate
formation in this system.