Biosynthetic Machinery of Diterpene Pleuromutilin Isolated from Basidiomycete Fungi

Momoka Yamane, Atsushi Minami, Chengwei Liu, Taro Ozaki, Ichiro Takeuchi, Tae Tsukagoshi, Tetsuo Tokiwano, Katsuya Gomi, Hideaki Oikawa

研究成果: Article査読

16 被引用数 (Scopus)

抄録

The diterpene pleuromutilin is a ribosome-targeting antibiotic isolated from basidiomycete fungi, such as Clitopilus pseudo-pinsitus. The functional characterization of all biosynthetic enzymes involved in pleuromutilin biosynthesis is reported and a biosynthetic pathway proposed. In vitro enzymatic reactions and mutational analysis revealed that a labdane-related diterpene synthase, Ple3, catalyzed two rounds of cyclization from geranylgeranyl diphosphate to premutilin possessing a characteristic 5–6–8-tricyclic carbon skeleton. Biotransformation experiments utilizing Aspergillus oryzae transformants possessing modification enzyme genes allowed the biosynthetic pathway from premutilin to pleuromutilin to be proposed. The present study sets the stage for the enzymatic synthesis of natural products isolated from basidiomycete fungi, which are a prolific source of structurally diverse and biologically active terpenoids.

本文言語English
ページ(範囲)2317-2322
ページ数6
ジャーナルChemBioChem
18
23
DOI
出版ステータスPublished - 2017 12 5

ASJC Scopus subject areas

  • 生化学
  • 分子医療
  • 分子生物学
  • 有機化学

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