Yamane Momoka, Minami Atsushi, Liu Chengwei, Ozaki Taro, Takeuchi Ichiro, Tsukagoshi Tae, Tokiwano Tetsuo, Gomi Katsuya, Oikawa Hideaki
Division of Chemistry, Graduate School of Science, Hokkaido University, Sapporo, 060-0810, Japan.
Graduate School of Agricultural Science, Tohoku University, Sendai, 981-8555, Japan.
Chembiochem. 2017 Dec 5;18(23):2317-2322. doi: 10.1002/cbic.201700434. Epub 2017 Oct 23.
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.
二萜类截短侧耳素是一种从担子菌纲真菌（如假丝盖伞）中分离出的靶向核糖体的抗生素。本文报道了截短侧耳素生物合成过程中所有生物合成酶的功能特性，并提出了一条生物合成途径。体外酶促反应和突变分析表明，一种与半日花烷相关的二萜合酶Ple3催化了两轮环化反应，从香叶基香叶基二磷酸生成具有特征性5-6-8三环碳骨架的前截短侧耳素。利用携带修饰酶基因的米曲霉转化体进行的生物转化实验，使得从前截短侧耳素到截短侧耳素的生物合成途径得以提出。本研究为从担子菌纲真菌中分离出的天然产物的酶促合成奠定了基础，担子菌纲真菌是结构多样且具有生物活性的萜类化合物的丰富来源。
