| 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 |
| lolitrem |
| 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 https://onlinelibrary.wiley.com/doi/10.1002/anie.202007280. 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) |
| URI: | http://hdl.handle.net/2115/82870 |
| 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)
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