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Structural basis of keto acid utilization in nonribosomal depsipeptide synthesis
Diego A Alonzo1, Clarisse Chiche-Lapierre1, Michael J Tarry1
1Department of Biochemistry and Centre de Recherche en Biologie Structurale, McGill University, Montreal, Quebec, Canada.
Abstract:
Nonribosomal depsipeptides are natural products composed of amino and hydroxy acid residues. The hydroxy acid residues often derive from α-keto acids, reduced by ketoreductase domains in the depsipeptide synthetases. Biochemistry and structures reveal the mechanism of discrimination for α-keto acids and a remarkable architecture: flanking intact adenylation and ketoreductase domains are sequences separated by >1,100 residues that form a split 'pseudoAsub' domain, structurally important for the depsipeptide module's synthetic cycle.
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