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
基金
中国国家自然科学基金; 国家重点研发计划;
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
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页数:8
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