Catalytic innovation underlies independent recruitment of polyketide synthases in cocaine and hyoscyamine biosynthesis

doi:10.1038/s41467-022-32776-1

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	Catalytic innovation underlies independent recruitment of polyketide synthases in cocaine and hyoscyamine biosynthesis
	Tian, Tian; Wang, Yong-Jiang; Huang, Jian-Ping; Li, Jie; Xu, Bingyan; Chen, Yin; Wang, Li; Yang, Jing; Yan, Yijun; Huang, Sheng-Xiong
	2022
发表期刊	NATURE COMMUNICATIONS
卷号	13 期号:1 页码:4994
摘要	Cocaine is a tropane alkaloid produced by Erythroxylum novogranatense. Here the authors identify two polyketide synthases involved in cocaine biosynthesis and provide insight into the parallel evolution of these enzymes in tropane alkaloids-producing plants. Tropane alkaloids such as hyoscyamine and cocaine are of importance in medicinal uses. Only recently has the hyoscyamine biosynthetic machinery become complete. However, the cocaine biosynthesis pathway remains only partially elucidated. Here we characterize polyketide synthases required for generating 3-oxo-glutaric acid from malonyl-CoA in cocaine biosynthetic route. Structural analysis shows that these two polyketide synthases adopt distinctly different active site architecture to catalyze the same reaction as pyrrolidine ketide synthase in hyoscyamine biosynthesis, revealing an unusual parallel/convergent evolution of biochemical function in homologous enzymes. Further phylogenetic analysis suggests lineage-specific acquisition of polyketide synthases required for tropane alkaloid biosynthesis in Erythroxylaceae and Solanaceae species, respectively. Overall, our work elucidates not only a key unknown step in cocaine biosynthesis pathway but also, more importantly, structural and biochemical basis for independent recruitment of polyketide synthases in tropane alkaloid biosynthesis, thus broadening the understanding of conservation and innovation of biosynthetic catalysts.
关键词	TROPANE ALKALOID BIOSYNTHESIS CHAIN-LENGTH CONTROL
DOI	10.1038/s41467-022-32776-1
收录类别	SCI
WOS记录号	WOS:000845603400016
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/74665
专题	中国科学院昆明植物研究所
推荐引用方式 GB/T 7714	Tian, Tian,Wang, Yong-Jiang,Huang, Jian-Ping,et al. Catalytic innovation underlies independent recruitment of polyketide synthases in cocaine and hyoscyamine biosynthesis[J]. NATURE COMMUNICATIONS,2022,13(1):4994.
APA	Tian, Tian.,Wang, Yong-Jiang.,Huang, Jian-Ping.,Li, Jie.,Xu, Bingyan.,...&Huang, Sheng-Xiong.(2022).Catalytic innovation underlies independent recruitment of polyketide synthases in cocaine and hyoscyamine biosynthesis.NATURE COMMUNICATIONS,13(1),4994.
MLA	Tian, Tian,et al."Catalytic innovation underlies independent recruitment of polyketide synthases in cocaine and hyoscyamine biosynthesis".NATURE COMMUNICATIONS 13.1(2022):4994.

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