How structural subtleties lead to molecular diversity for the type III polyketide synthases

Hiroyuki Morita*, Chin Piow Wong, Ikuro Abe

*この論文の責任著者

研究成果: ジャーナルへの寄稿総説査読

63 被引用数 (Scopus)

抄録

Type III polyketide synthases (PKSs) produce an incredibly diverse group of plant specialized metabolites with medical importance despite their structural simplicity compared with the modular type I and II PKS systems. The type III PKSs use homodimeric proteins to construct the molecular scaffolds of plant polyketides by iterative condensations of starter and extender CoA thioesters. Ever since the structure of chalcone synthase (CHS) was disclosed in 1999, crystallographic and mutational studies of the type III PKSs have explored the intimate structural features of these enzyme reactions, revealing that seemingly minor alterations in the active site can drastically change the catalytic functions and product profiles. New structures described in this review further build on this knowledge, elucidating the detailed catalytic mechanism of enzymes that make curcuminoids, use extender substrates without the canonical CoA activator, and use noncanonical starter substrates, among others. These insights have been critical in identifying structural features that can serve as a platform for enzyme engineering via structure-guided and precursor-directed engineered biosynthesis of plant polyketides. In addition, we describe the unique properties of the recently discovered "second-generation" type III PKSs that catalyzes the one-pot formation of complex molecular scaffolds from three distinct CoA thioesters or from "CoA-free" substrates, which are also provid-ingexciting new opportunities for synthetic biology approaches. Finally, we consider post-type III PKS tailoring enzymes, which can also serve as useful tools for combinatorial biosynthesis of further unnatural novel molecules. Recent progress in the field has led to an exciting time of understanding and manipulating these fascinating enzymes.

本文言語英語
ページ(範囲)15121-15136
ページ数16
ジャーナルJournal of Biological Chemistry
294
41
DOI
出版ステータス出版済み - 2019/10/11

ASJC Scopus 主題領域

  • 生化学
  • 分子生物学
  • 細胞生物学

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