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Heterologous Biosynthesis of Fungal Indole Sesquiterpene Sespendole
Author(s) -
Kudo Kosei,
Liu Chengwei,
Matsumoto Tomoyuki,
Minami Atsushi,
Ozaki Taro,
Toshima Hiroaki,
Gomi Katsuya,
Oikawa Hideaki
Publication year - 2018
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.201800187
Subject(s) - biosynthesis , sesquiterpene , heterologous , indole test , chemistry , biochemistry , stereochemistry , enzyme , gene
Indole sesquiterpene sespendole, which has been isolated from the filamentous fungus Pseudobotrytis terrestris FKA‐25, is a specific inhibitor of lipid droplet synthesis in mouse macrophages. The biosynthetic pathway that involves genes encoding six enzymes ( spdEMBQHJ ) was elucidated through heterologous expression of spd genes in Aspergillus oryzae , biotransformation experiments, and in vitro enzymatic reactions with a recombinant protein, thereby revealing the mechanism underlying the characteristic modification on the indole ring, catalyzed by a set of prenyltransferase (SpdE)/cytochrome P450 (SpdJ) enzymes. Functional analysis of the homologous genes encoding these enzymes involved in the biosynthesis of lolitrem allowed a biosynthetic pathway for the bicyclic ring skeleton fused to the indole ring to be proposed.