Harnessing the catalytic plasticity of the ent-kaurene synthase from Bradyrhizobium japonicum to produce the ent-rosane and ent-pimarane scaffolds

被引：2

作者：

Zhang, Fan ^{[2
,4
]}

Wang, Su-Jing ^{[1
]}

Xiao, Wen ^{[1
]}

Yu, Ming-Zhu ^{[1
]}

Sha, Feng ^{[1
]}

Wu, Ruibo ^{[2
]}

Xiang, Zheng ^{[1
,3
]}

机构：

[1] Peking Univ, Sch Chem Biol & Biotechnol, Shenzhen Grad Sch, AI Sci Preferred AI4S Program,State Key Lab Chem O, Shenzhen 518055, Peoples R China

[2] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangdong Prov Key Lab New Drug Design & Evaluat, Guangzhou 510006, Peoples R China

[3] Inst Chem Biol, Gaoke Innovat Ctr, Shenzhen Bay Lab, Guangqiao Rd, Shenzhen 518132, Peoples R China

[4] Guangzhou Univ Chinese Med, Int Inst Translat Chinese Med, Sch Pharmaceut Sci, Guangdong Prov Key Lab Translat Canc Res Chinese M, Guangzhou 510006, Peoples R China

来源：

CATALYSIS SCIENCE & TECHNOLOGY | 2024年 / 14卷 / 02期

基金：

中国国家自然科学基金;

关键词：

MAIN-GROUP THERMOCHEMISTRY; SINGLE RESIDUE SWITCH; LANOSTEROL BIOSYNTHESIS; DITERPENE SYNTHASES; C-RING; INTERMEDIATE; TRACHYLOBANE; CYCLIZATION; EVOLUTION; ATISERENE;

D O I：

10.1039/d3cy00115f

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070304 ; 081704 ;

摘要：

The ent-kaurene synthase catalyses the formation of ent-kaurene through a multistep cyclization process, which is an essential step in the biosynthesis of many bioactive natural products. Channeling the key carbocation intermediates through different reaction pathways offers access to different diterpene scaffolds. Herein, we report that the F72Y mutation of the ent-kaurene synthase from Bradyrhizobium japonicum leads to the formation of tricyclic ent-rosa-5(10),15-diene and ent-pimara-8,15-diene as well as tetracyclic ent-kaurene. The combined computational and experimental studies suggest that Tyr72 serves as a general base for reshaping the catalytic function. This finding provides a promiscuous synthase for further engineering to improve its activity and selectivity, which can be used in the heterologous synthesis of ent-rosane and ent-pimarane diterpenoids.

引用

页码：306 / 314

页数：9