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

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2317-2322
Number of pages6
JournalChemBioChem
Volume18
Issue number23
DOIs
Publication statusPublished - 2017 Dec 5

Keywords

  • biosynthesis
  • fungi
  • gene expression
  • natural products
  • terpenoids

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

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    Yamane, M., Minami, A., Liu, C., Ozaki, T., Takeuchi, I., Tsukagoshi, T., Tokiwano, T., Gomi, K., & Oikawa, H. (2017). Biosynthetic Machinery of Diterpene Pleuromutilin Isolated from Basidiomycete Fungi. ChemBioChem, 18(23), 2317-2322. https://doi.org/10.1002/cbic.201700434