Characterization of Giant Modular PKSs Provides Insight into Genetic Mechanism for Structural Diversification of Aminopolyol Polyketides. Issue 7 (11th January 2017)

• Record Type: Journal Article
• Authors: Zhang, Lihan; Hashimoto, Takuya; Qin, Bin; Hashimoto, Junko; Kozone, Ikuko; Kawahara, Teppei; Okada, Masahiro; Awakawa, Takayoshi; Ito, Takuya; Asakawa, Yoshinori; Ueki, Masashi; Takahashi, Shunji; Osada, Hiroyuki; Wakimoto, Toshiyuki; Ikeda, Haruo; Shin‐ya, Kazuo; Abe, Ikuro
• Is Part Of: Angewandte Chemie international edition. Volume 56:Issue 7(2017)
• Page Start: 1740
• Page End: 1745
• Publication Date: 2017-01-11
• Subjects: bioengineering -- biosynthesis -- polyketides -- protein structures; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201611371
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Polyketides form many clinically valuable compounds. However, manipulation of their biosynthesis remains highly challenging. An understanding of gene cluster evolution provides a rationale for reprogramming of the biosynthetic machinery. Herein, we report characterization of giant modular polyketide synthases (PKSs) responsible for the production of aminopolyol polyketides. Heterologous expression of over 150 kbp polyketide gene clusters successfully afforded their products, whose stereochemistry was established by taking advantage of bioinformatic analysis. Furthermore, phylogenetic analysis of highly homologous but functionally diverse domains from the giant PKSs demonstrated the evolutionary mechanism for structural diversification of polyketides. The gene clusters characterized herein, together with their evolutionary insights, are promising genetic building blocks for de novo production of unnatural polyketides. Abstract : Module swapping : Aminopolyols are a class of bioactive polyketides biosynthesized by giant modular polyketide synthases (PKSs). Heterologous expression of over 150 kbp PKS gene clusters afforded novel aminopolyols, and phylogenetic comparison of four aminopolyol PKS gene clusters illustrated the precise mechanism of PKS reprogramming in nature.