Editing function of type Ⅱ thioesterases in the biosynthesis of fungal polyketides  

作　　者：Fenglin Jiang Anan Liu Qian Wei Youcai Hu 

机构地区：[1]State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China

出　　处：《Chinese Chemical Letters》2024年第10期325-328,共4页中国化学快报（英文版）

基　　金：supported financially by the National Natural Science Foundation of China(Nos.82225042,T2192973);the CAMS Innovation Fund for Medical Sciences(No.CIFMS 2021-I2M1-029)。

摘　　要：Polyketide synthases(PKSs)are megasynthases with multiple autonomously folding domains,which operate cooperatively in the PKS assemblies to synthesize specific polyketide scaffolds.Any nonreactive intermediates tethered to acyl carrier protein(ACP)domain in the PKS will block the elongation process of polyketide chains.In this study,we systematically elucidate the editing function of fungal typeⅡthioesterases(TEIIs)to hydrolyze ACP domain-bounded nonreactive acyl groups,which are uploaded by substrate promiscuous fungal phosphopantetheinyl transferase.Thereof,the TEIIs encoded in gene clusters of nonreducing PKS with reductase domain exhibit universal editing function.Besides,editing function was also found for TEIIs encoded in gene clusters of highly-reducing PKS with condensation domain.Hence,the editing TEIIs with function of recovery PKS are applied to improve the yield of the fungal polyketides in vivo.Our study provides valuable insights into the editing process of fungal PKSs,highlights the crucial role of TEIIs in enhancing polyketide production and introduces a novel metabolic engineering strategy for fungal polyketide biosynthesis by leveraging the editing function of TEIIs.

关 键 词：Editing enzyme Type II thioesterase BIOSYNTHESIS Polyketide synthase Metabolic engineering 

分 类 号：Q78[生物学—分子生物学]