HUSCAP logo Hokkaido Univ. logo

Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Science / Faculty of Science >
Peer-reviewed Journal Articles, etc >

Biosynthesis of Indole Diterpene Lolitrems : Radical-Induced Cyclization of an Epoxyalcohol Affording a Characteristic Lolitremane Skeleton

Files in This Item:
Angew. Chem.-Int. Edit.59-41_17996-18002.pdf555.72 kBPDFView/Open
Please use this identifier to cite or link to this item:

Title: Biosynthesis of Indole Diterpene Lolitrems : Radical-Induced Cyclization of an Epoxyalcohol Affording a Characteristic Lolitremane Skeleton
Authors: Jiang, Yulu Browse this author
Ozaki, Taro Browse this author
Harada, Mei Browse this author
Miyasaka, Tadachika Browse this author
Sato, Hajime Browse this author
Miyamoto, Kazunori Browse this author
Kanazawa, Junichiro Browse this author
Liu, Chengwei Browse this author
Maruyama, Jun-ichi Browse this author
Adachi, Masaatsu Browse this author
Nakazaki, Atsuo Browse this author
Nishikawa, Toshio Browse this author
Uchiyama, Masanobu Browse this author
Minami, Atsushi Browse this author
Oikawa, Hideaki Browse this author →KAKEN DB
Keywords: cyclization
cytochrome P450
natural products
radical reactions
Issue Date: 5-Oct-2020
Publisher: Wiley-Blackwell
Journal Title: Angewandte chemie-international edition
Volume: 59
Issue: 41
Start Page: 17996
End Page: 18002
Publisher DOI: 10.1002/anie.202007280
Abstract: Lolitrems are tremorgenic indole diterpenes that exhibit a unique 5/6 bicyclic system of the indole moiety. Although genetic analysis has indicated that the prenyltransferase LtmE and the cytochrome P450 LtmJ are involved in the construction of this unique structure, the detailed mechanism remains to be elucidated. Herein, we report the reconstitution of the biosynthetic pathway for lolitrems employing a recently established genome-editing technique for the expression host Aspergillus oryzae. Heterologous expression and bioconversion of the various intermediates revealed that LtmJ catalyzes multistep oxidation to furnish the lolitrem core. We also isolated the key reaction intermediate with an epoxyalcohol moiety. This observation allowed us to establish the mechanism of radical-induced cyclization, which was firmly supported by density functional theory calculations and a model experiment with a synthetic analogue.
Rights: This is the peer reviewed version of the following article: Angewandte chemie-international edition 59(41) October 5 2020, pp.17996-18002, which has been published in final form at This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
Type: article (author version)
Appears in Collections:理学院・理学研究院 (Graduate School of Science / Faculty of Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 及川 英秋

Export metadata:

OAI-PMH ( junii2 , jpcoar_1.0 )

MathJax is now OFF:


 - Hokkaido University