蛋白酶体抑制剂Syrbactins家族的生物合成

Advances in biosynthesis of proteasome inhibitor syrbactins

摘要:

微生物来源的syrbactins属于十二元内酰胺短肽类化合物，包括丁香霉素（syringolins）、滑杆菌素（glidobactins）、cepafungins和luminmycins等。其中，syringolins、glidobactins、luminmycins等几个化合物生物合成基因簇已被克隆、测序和异源表达。研究发现它们的十二元内酰胺环骨架都是由非核糖体肽合成酶（NRPS）-聚酮合酶（PKS）复合体采用模块化组装的方式，将系列底物组装而成。这类化合物因具有优异的蛋白酶体抑制活性而受到广泛关注。本文从syrbactins的分子结构、生物合成、作用机理等几个方面进行综述，介绍了近年来syrbactins的研究进展。

Abstract:

Syrbactins are microbial natural products, mainly composed of syringolins, glidobactins, cepafunins and luminmycins. At present, several biosynthetic gene clusters of syringolins and other compounds have been cloned, sequenced and heterologously expressed. These studies revealed that, despite the structural differences between syrbactins, they are synthesized in vivo in a similar mode and share a NRPS-PKS hybrid assembly biosynthetic pathway for the formation of their core skeletons. They have drawn continuous research attentions due to the irreversible proteasome inhibition activity. This review focuses on the research advances in syrbactins and highlights their structure, biosynthesis and mode-of-action.