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| 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 | |
| Source Publication | ACS CHEMICAL BIOLOGY
 |
| ISSN | 1554-8937 |
| Abstract | 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. |
| Keyword | CRYSTAL-STRUCTURE GENOMES |
| Subject Area | Biochemistry & Molecular Biology |
| DOI | 10.1021/acschembio.2c00739 |
| Indexed By | SCI |
| WOS ID | WOS:000914871900001 |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.kib.ac.cn/handle/151853/75278 |
| Collection | 中国科学院昆明植物研究所 |
| Recommended Citation 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). |
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| 10.1021_acschembio.2（4470KB） | 期刊论文 | 出版稿 | 开放获取 | CC BY-NC-SA | View Download | |
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