Recent advances in the structural analysis of adenylation domains in natural product biosynthesis
Recent advances in the structural analysis of adenylation domains in natural product biosynthesis
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天然产物生物合成中腺苷酸化结构域结构分析的最新进展
DOI：
10.1016/j.cbpa.2022.102212
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发表时间：
2022
影响因子：
7.8
通讯作者：
Eguchi Tadashi
中科院分区：
文献类型：
--
作者：
Miyanaga Akimasa;Kudo Fumitaka;Eguchi Tadashi
腺苷酸化（A）结构域通过选择性地将酰基底物转移到同源载体蛋白（CP）上来催化酰基结构单元到非核糖体肽和相关天然产物中的生物合成掺入。A结构域使用非典型酰基单元，如非蛋白质氨基酸和酮酸，扩展了天然产物的结构多样性。此外，具有嵌入的辅助结构域的中断的A结构域能够修饰并入的酰基单元。A结构域上的结构信息对于合理的蛋白质工程产生非天然化合物是重要的。本文综述了A结构域结构分析的最新进展。首先，我们讨论了A结构域识别非典型酰基单元的机制。然后，我们专注于与CP域和嵌入的辅助域的A域的相互作用。
Adenylation (A) domains catalyze the biosynthetic incorporation of acyl building blocks into nonribosomal peptides and related natural products by selectively transferring acyl substrates onto cognate carrier proteins (CP). The use of noncanonical acyl units, such as nonproteinogenic amino acids and keto acids, by A domains expands the structural diversity of natural products. Furthermore, interrupted A domains, which have embedded auxiliary domains, are able to modify the incorporated acyl units. Structural information on A domains is important for rational protein engineering to generate unnatural compounds. In this review, we summarize recent advances in the structural analysis of A domains. First, we discuss the mechanisms by which A domains recognize noncanonical acyl units. We then focus on the interactions of A domains with CP domains and embedded auxiliary domains.