Department of Biochemistry and Centre de Recherche en Biologie Structurale, McGill University, Montreal, Quebec, Canada.
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.
Nat Chem Biol. 2020 May;16(5):493-496. doi: 10.1038/s41589-020-0481-5. Epub 2020 Feb 17.
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 'pseudoA' domain, structurally important for the depsipeptide module's synthetic cycle.
非核糖体衍生的环二肽是由氨基酸和羟酸残基组成的天然产物。羟酸残基通常来自α-酮酸，由环二肽合成酶中的酮还原酶结构域还原。生物化学和结构揭示了α-酮酸的识别机制和显著的结构：侧翼完整的氨酰化酶和酮还原酶结构域之间是由>1100 个残基隔开的序列，形成一个分裂的“伪 A”结构域，对于环二肽模块的合成循环具有重要的结构意义。
