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Identification and Characterization of a Methionine γ‐Lyase in the Calicheamicin Biosynthetic Cluster of Micromonospora echinospora
Author(s) -
Song Haigang,
Xu Ri,
Guo Zhihong
Publication year - 2015
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201402489
Subject(s) - lyase , methionine , active site , biosynthesis , biochemistry , cystathionine beta synthase , micromonospora , stereochemistry , methanethiol , enzyme , methionine synthase , chemistry , cofactor , methionine sulfoxide reductase , amino acid , biology , sulfur , bacteria , organic chemistry , streptomyces , genetics
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 γ‐lyases and cystathionine γ‐synthases. However, it was found to be active towards methionine and to convert this amino acid into α‐ketobutyrate, ammonium, and methanethiol. The crystal structure of the cofactor‐bound holoenzyme was resolved at 2.0 Å; it contains two active site residues, Gly105 and Val322, specific for methionine γ‐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 γ‐lyase producing methanethiol as a building block in biosynthesis of calicheamicins.