链霉菌磷酸泛酰巯基乙胺基转移酶对载体蛋白的底物选择性的研究进展

Substrate specificity of phosphopantetheinyl transferases to carrier proteins in Streptomyces

摘要:

近年来组合生物学技术在开发抗生素类似物的研究中发挥着越来越重要的作用，在他克莫司类似物的组合生物合成中，通过应用外源合成前体取代烯丙基丙二酸单酰基和4,5-二羟基-1-烯-环己甲酸，以及应用模块化合成元件取代AM合成元件和改造后修饰合成元件，已经生产出11个他克莫司类似物，这些研究拓宽了人们对标准化合成前体和模块化合成元件的认识，为通过组合生物合成手段进行抗生素的更新换代提供指导。

Abstract:

Phosphopantetheinyl transferases (PPTases) play essential role in the biosynthesis of fatty acids, polyketides, and nonribosomal peptides. PPTases phosphopantetheinylate carrier proteins in polyketide synthases (PKSs), fatty acid synthases (FASs) and nonribosomal peptide synthetases (NRPSs). In this review, we discuss current studies on the substrate specificities of PPTases to carrier proteins in Streptomyces. The substrates of type Ⅲ PPTases are acyl carrier proteins (ACPs) which locate within the same PKSs. The favorite substrates of typeⅠ PPTases are ACPs in typeⅡ FASs and typeⅡ PKSs. The favorite substrates of typeⅡ PPTases are ACPs in typeⅠ PKSs and peptidyl carrier proteins (PCPs) in NRPSs. The favorite substrates of a typeⅠ/Ⅱ PPTase, whose encoding gene locates in a gene cluster, are ACPs/PCPs whose encoding genes locate in the same gene cluster.