Depsipeptides are compounds that contain both ester bonds and amide bonds. Important natural product depsipeptides include the piscicide antimycin, the K⁺ ionophores cereulide and valinomycin, the anticancer agent cryptophycin, and the antimicrobial kutzneride. Furthermore, database searches return hundreds of uncharacterized systems likely to produce novel depsipeptides. These compounds are made by specialized nonribosomal peptide synthetases (NRPSs). NRPSs are biosynthetic megaenzymes that use a module architecture and multi‐step catalytic cycle to assemble monomer substrates into peptides, or in the case of specialized depsipeptide synthetases, depsipeptides. Two NRPS domains, the condensation domain and the thioesterase domain, catalyze ester bond formation, and ester bonds are introduced into depsipeptides in several different ways. The two most common occur during cyclization, in a reaction between a hydroxy‐containing side chain and the C‐terminal amino acid residue in a peptide intermediate, and during incorporation into the growing peptide chain of an α‐hydroxy acyl moiety, recruited either by direct selection of an α‐hydroxy acid substrate or by selection of an α‐keto acid substrate that is reduced in situ. In this article, we discuss how and when these esters are introduced during depsipeptide synthesis, survey notable depsipeptide synthetases, and review insight into bacterial depsipeptide synthetases recently gained from structural studies.

中文翻译：

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depsipeptides 或 Depsi 的生物合成：具有不同世代的肽

缩肽是同时含有酯键和酰胺键的化合物。重要的天然产物缩肽包括杀鱼剂抗霉素、K ⁺离子载体脑蜡和缬氨霉素、抗癌剂隐藻素和抗菌库兹奈德。此外，数据库搜索会返回数百个可能产生新缩肽的未表征系统。这些化合物由专门的非核糖体肽合成酶 (NRPS) 制成。NRPS 是生物合成巨酶，它使用模块结构和多步催化循环将单体底物组装成肽，或者在专门的缩肽合成酶的情况下，缩肽。两个 NRPS 结构域，即缩合结构域和硫酯酶结构域，催化酯键的形成，并且酯键以几种不同的方式引入缩肽。最常见的两种情况发生在环化过程中，即含羟基的侧链与肽中​​间体的 C 端氨基酸残基之间的反应中，并在并入不断增长的 α-羟基酰基部分的肽链期间，通过直接选择 α-羟基酸底物或选择原位还原的 α-酮酸底物来募集。在本文中，我们讨论了在缩酚酸合成过程中如何以及何时引入这些酯，调查了显着的缩酚酸合成酶，并回顾了最近从结构研究中获得的对细菌缩酚酸合成酶的见解。