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 journalArticlepeer-review

    17 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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