Guvermectin Biosynthesis Revealing the Key Role of a Phosphoribohydrolase and Structural Insight into the Active Glutamate of a Noncanonical Adenine Phosphoribosyltransferase

doi:10.1021/acschembio.2c00739

KIB OpenIR

	Guvermectin Biosynthesis Revealing the Key Role of a Phosphoribohydrolase and Structural Insight into the Active Glutamate of a Noncanonical Adenine Phosphoribosyltransferase
	Liu,Chongxi; Wang,Zhiyan; Chen,Yin; Yan,Yijun; Li,Lei; Wang,Yong-Jiang; Bai,Lu; Li,Shanshan; Zhang,Yanyan; Wang,Xiangjing; Huang,Sheng-Xiong; Xiang,Wensheng
	2023
发表期刊	ACS CHEMICAL BIOLOGY
ISSN	1554-8937
摘要	Guvermectin is a novel plant growth regulator that has been registered as a new agrochemical in China. It is an adenosine analogue with an unusual psicofuranose instead of ribose. Herein, the gene cluster responsible for guvermectin biosynthesis in Streptomyces caniferus NEAU6 is identified using gene interruption and heterologous expression experiments. A key intermediate psicofuranine 6 '-phosphate (PMP) is chemically synthesized, and the functions of GvmB, C, D, and E are verified by individual stepwise enzyme reactions in vitro. The results also show that the biosynthesis of guvermectin is coupled with adenosine production by a single cluster. The higher catalytic efficiency of GvmB on PMP than AMP ensures the effective biosynthesis of guvermectin. Moreover, a phosphoribohydrolase GvmA is employed in the pathway that can hydrolyze AMP but not PMP and shows higher catalytic efficiency for the AMP hydrolysis than that of the AMP dephosphorylation by GvmB, leading to shunting of adenosine biosynthesis toward the production of guvermectin. Finally, the crystal structure of GvmE in complex with the product PMP has been solved. Glu160 at the C-terminal is identified as the acid/base for protonation/deprotonation of N7 of the adenine ring, demonstrating that GvmE is a noncanonical adenine phosphoribosyltransferase.
关键词	CRYSTAL-STRUCTURE GENOMES
学科领域	Biochemistry & Molecular Biology
DOI	10.1021/acschembio.2c00739
收录类别	SCI
WOS记录号	WOS:000914871900001
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/75278
专题	中国科学院昆明植物研究所
推荐引用方式 GB/T 7714	Liu,Chongxi,Wang,Zhiyan,Chen,Yin,et al. Guvermectin Biosynthesis Revealing the Key Role of a Phosphoribohydrolase and Structural Insight into the Active Glutamate of a Noncanonical Adenine Phosphoribosyltransferase[J]. ACS CHEMICAL BIOLOGY,2023.
APA	Liu,Chongxi.,Wang,Zhiyan.,Chen,Yin.,Yan,Yijun.,Li,Lei.,...&Xiang,Wensheng.(2023).Guvermectin Biosynthesis Revealing the Key Role of a Phosphoribohydrolase and Structural Insight into the Active Glutamate of a Noncanonical Adenine Phosphoribosyltransferase.ACS CHEMICAL BIOLOGY.
MLA	Liu,Chongxi,et al."Guvermectin Biosynthesis Revealing the Key Role of a Phosphoribohydrolase and Structural Insight into the Active Glutamate of a Noncanonical Adenine Phosphoribosyltransferase".ACS CHEMICAL BIOLOGY (2023).

条目包含的文件		下载所有文件
文件名称/大小	文献类型	版本类型	开放类型	使用许可
10.1021_acschembio.2（4470KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	浏览下载