CRYSTALLISATION AND PRELIMINARY STRUCTURAL ANALYSIS OF ECM18 WHICH CATALYSES DISULFIDE TO THIOACETAL CONVERSION IN ECHINOMYCIN BIOSYNTHESIS

Abstract

Echinomycin, produced by the soil bacterium Streptomyces lasaliensis, is a non-ribosomal peptide natural product with both antibiotic and antitumor activity. In the first step of echinomycin biosynthesis, two non-ribosomal peptide synthetases produce the eight-residue cyclic peptide scaffold. In the next step, a disulfide bridge is formed across the peptide scaffold which is then converted to a thioacetal group by the enzyme Ecm18. This thioacetal group confers extra structural rigidity and chemical stability to echinomycin which is important for maintaining its biological activity. We report a preliminary X-ray crystal structure of the Ecm18¿echinomycin¿S-adenosylhomocysteine ternary complex and provide a plausible catalytic mechanism.