Tropane alkaloids biosynthesis involves an unusual type III polyketide synthase and non-enzymatic condensation

被引：42

作者：

Huang, Jian-Ping ^{[1
,2
]}

Fang, Chengli ^{[3
,4
]}

Ma, Xiaoyan ^{[1
,2
,5
]}

Wang, Li ^{[1
,2
]}

Yang, Jing ^{[1
,2
]}

Luo, Jianying ^{[1
,2
]}

Yan, Yijun ^{[1
,2
]}

Zhang, Yu ^{[3
,4
]}

Huang, Sheng-Xiong ^{[1
,2
]}

机构：

[1] Chinese Acad Sci, State Key Lab Phytochem & Plant Resources West Ch, Kunming Inst Bot, Kunming 650201, Yunnan, Peoples R China

[2] Chinese Acad Sci, CAS Ctr Excellence Mol Plant Sci, Kunming Inst Bot, Kunming 650201, Yunnan, Peoples R China

[3] Chinese Acad Sci, Key Lab Synthet Biol, Inst Plant Physiol & Ecol, Shanghai 200032, Peoples R China

[4] Chinese Acad Sci, CAS Ctr Excellence Mol Plant Sci, Inst Plant Physiol & Ecol, Shanghai 200032, Peoples R China

[5] Sichuan Univ Sci & Engn, Sch Chem & Chem Engn, Zigong 643000, Peoples R China

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

国家重点研发计划; 中国国家自然科学基金;

关键词：

CHAIN-LENGTH CONTROL; HAIRY ROOT CULTURES; METHYLPUTRESCINE OXIDASE; ENGINEERED BIOSYNTHESIS; PLANT POLYKETIDES; DATURA-STRAMONIUM; NATURAL-PRODUCTS; INTERMEDIATE; ORNITHINE; COCAINE;

D O I：

10.1038/s41467-019-11987-z

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The skeleton of tropane alkaloids is derived from ornithine-derived N-methylpyrrolinium and two malonyl-CoA units. The enzymatic mechanism that connects N-methylpyrrolinium and malonyl-CoA units remains unknown. Here, we report the characterization of three pyrrolidine ketide synthases (PYKS), AaPYKS, DsPYKS, and AbPYKS, from three different hyoscyamine- and scopolamine- producing plants. By examining the crystal structure and biochemical activity of AaPYKS, we show that the reaction mechanism involves PYKS-mediated malonyl-CoA condensation to generate a 3-oxo-glutaric acid intermediate that can undergo non-enzymatic Mannich-like condensation with N-methylpyrrolinium to yield the racemic 4-(1-methyl-2-pyrrolidinyl)-3-oxobutanoic acid. This study therefore provides a long sought-after biosynthetic mechanism to explain condensation between N-methylpyrrolinium and acetate units and, more importantly, identifies an unusual plant type III polyketide synthase that can only catalyze one round of malonyl- CoA condensation.

引用

页数：8