Identification and Characterization of a Methionine γ-Lyase in the Calicheamicin Biosynthetic Cluster of Micromonospora echinospora

CalE6 is a previously uncharacterized protein involved in the biosynthesis of calicheamicins in Micromonospora echinospora. It is a pyridoxal-5'-phosphate-dependent enzyme and exhibits high sequence homology to cystathionine gamma-lyases and cystathionine g-synthases. However, it was found to be active towards methionine and to convert this amino acid into a-ketobutyrate, ammonium, and methanethiol. The crystal structure of the cofactor-bound holoenzyme was resolved at 2.0 (A) over cap; it contains two active site residues, Gly105 and Val322, specific for methionine gamma-lyases. Modeling of methionine into the active site allows identification of the active site residues responsible for substrate recognition and catalysis. These findings support that CalE6 is a putative methionine gamma-lyase producing methanethiol as a building block in biosynthesis of calicheamicins.