Reconstitution of a New Cysteine Biosynthetic Pathway inMycobacteriumtuberculosis

Abstract

A new pathway for cysteine biosynthesis has been elucidated in Mycobacterium tuberculosis. This pathway involves a protein-bound thiocarboxylate (CysO−SH) as the sulfide donor, similar to thiamin biosynthesis. Cysteine synthase M (CysM) catalyzes the addition of cysteine to the carboxy terminus of the protein-bound thiocarboxylate to generate a CysO−cysteine adduct. A protease, Mec⁺, hydrolyzes the CysO−cysteine adduct to release cysteine and regenerate CysO. Mec⁺ contains a JAMM motif, and this work provides the first functional characterization of the JAMM motif in prokaryotes. MoeZ, a paralogue of ThiF, has been shown to transfer sulfur onto CysO.