Abstract:

<p>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 &gt;1,100 residues that form a split &#39;pseudoA&#39; domain, structurally important for the depsipeptide module&#39;s synthetic cycle.</p>