Identification and Characterization of a Methionine γ‐Lyase in the Calicheamicin Biosynthetic Cluster of Micromonospora echinospora. Issue 1 (17th November 2014)

• Record Type: Journal Article
• Authors: Song, Haigang; Xu, Ri; Guo, Zhihong
• Is Part Of: Chembiochem. Volume 16:Issue 1(2015)
• Page Start: 100
• Page End: 109
• Publication Date: 2014-11-17
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201402489
• Languages: English
• ISSNs: 1439-4227

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>CalE6 is a previously uncharacterized protein involved in the biosynthesis of calicheamicins in <italic>Micromonospora echinospora</italic>. 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.</p> </abstract>