In vitro reconstitution of a PKS pathway for the biosynthesis of galbonolides in Streptomyces sp. LZ35

Chembiochem : a European Journal of Chemical Biology
Chao LiuYuemao Shen

Abstract

The galbonolides are 14-membered macrolide antibiotics with a macrocyclic backbone similar to that of erythromycins. Galbonolides exhibit broad-spectrum antifungal activities. Retro-biosynthetic analysis suggests that the backbone of galbonolides is assembled by a type I modular polyketide synthase (PKS). Unexpectedly, the galbonolide biosynthetic gene cluster, gbn, in Streptomyces sp. LZ35 encodes a hybrid fatty acid synthase (FAS)-PKS pathway. In vitro reconstitution revealed the functions of GbnA (an AT-ACP didomain protein), GbnC (a FabH-like enzyme), and GbnB (a novel multidomain PKS module without AT and ACP domains) responsible for assembling the backbone of galbonolides, respectively. To our knowledge, this study is the first biochemical characterization of a hybrid FAS-PKS pathway for the biosynthesis of 14-membered macrolides. The identification of this pathway provides insights into the evolution of PKSs and could facilitate the design of modular pools for synthetic biology.

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Citations

Jan 27, 2017·Chemical Communications : Chem Comm·Marie E YurkovichPeter F Leadlay
Mar 5, 2015·Antonie van Leeuwenhoek·Chao LiuYuemao Shen
Dec 2, 2017·Chembiochem : a European Journal of Chemical Biology·Jianxiong WangYuemao Shen
Sep 1, 2020·Angewandte Chemie·Guifa ZhaiYuhui Sun

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