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Characterization of Giant Modular PKSs Provides Insight into Genetic Mechanism for Structural Diversification of Aminopolyol Polyketides
Author(s) -
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,
Shinya Kazuo,
Abe Ikuro
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201611371
Subject(s) - polyketide , biology , gene cluster , gene , computational biology , phylogenetic tree , mechanism (biology) , genetics , biosynthesis , philosophy , epistemology
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.