Characterization of Giant Modular PKSs Provides Insight into Genetic Mechanism for Structural Diversification of Aminopolyol Polyketides
Characterization of Giant Modular PKSs Provides Insight into Genetic Mechanism for Structural Diversification of Aminopolyol Polyketides
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DOI：
10.1002/anie.201611371
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发表时间：
2017-02-06
影响因子：
16.6
通讯作者：
Abe, Ikuro
中科院分区：
文献类型：
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作者：
Zhang, Lihan;Hashimoto, Takuya;Abe, Ikuro
聚酮化合物形成许多具有临床价值的化合物。然而，操纵其生物合成仍然具有高度挑战性。对基因簇进化的理解为生物合成机制的重新编程提供了理论基础。在这里，我们报告的巨型模块化聚酮酶（PKSs）负责生产氨基多元醇聚酮的表征。利用生物信息学分析方法，对150 kbp以上的聚酮基因簇进行了立体化学分析，并成功地进行了异源表达。此外，系统发育分析的高度同源，但功能多样的结构域从巨大的PKS证明了聚酮化合物的结构多样化的进化机制。本文表征的基因簇，连同它们的进化见解，是用于从头生产非天然聚酮化合物的有希望的遗传构建块。
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 denovo production of unnatural polyketides.