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Biosynthetic Machinery of Diterpene Pleuromutilin Isolated from Basidiomycete Fungi
Author(s) -
Yamane Momoka,
Minami Atsushi,
Liu Chengwei,
Ozaki Taro,
Takeuchi Ichiro,
Tsukagoshi Tae,
Tokiwano Tetsuo,
Gomi Katsuya,
Oikawa Hideaki
Publication year - 2017
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201700434
Subject(s) - diterpene , aspergillus oryzae , biosynthesis , enzyme , terpenoid , biology , biochemistry , chemistry , labdane , biotransformation , stereochemistry
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.