文献类型：期刊文献

英文题名：The importance of selecting crystal form for triazole fungicide tebuconazole to enhance its botryticidal activity

作者：Chen, Yongjun[1];Yan, Dongmei[1];Xu, Jialin[1];Xiong, Hui[1];Luan, Shaorong[2];Xiao, Ciying[3];Huang, Qingchun[1]

机构：[1]East China Univ Sci & Technol, Shanghai Key Lab Chem Biol, Sch Pharm, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Chem & Mol Engn, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Sch Biol Engn, Shanghai 200237, Peoples R China

年份：2023

卷号：854

外文期刊名：SCIENCE OF THE TOTAL ENVIRONMENT

收录：;EI(收录号：20223812778095);WOS:【SCI-EXPANDED(收录号:WOS:000884231200002)】；

基金：This work was supported in part by the Project of the Innovation Action Plan of the Shanghai Science and Technology Committee of China (No. 21S11901400, 22N41900100).

语种：英文

外文关键词：Tebuconazole; Crystal form; Fungicidal activity; TCA metabolism; Point mutation; Botrytis cinerea

摘要：The growing evidences of resistant fungi stimulate fully understanding tebuconazole regarding its crystal structure on fungicidal activity. In this study, the crystal structures of six technical tebuconazoles (BX, HH, JP, QZ, SJ, and YT) were characterized by using high-resolution X-ray powder diffraction and three-dimensional crystal structure modeling. A structure-activity relationship of the tebuconazoles on the susceptible (HLS and YJS) or resistant (XHR) Botrytis cinerea isolates was analyzed, the differential tricarboxylic acid (TCA) cycle metabolism was determined, and molecular docking with sterol 14 alpha-demethylase (CYP51) was performed. The results showed that tebuconazole existed in three types of crystal forms: an overlapping-pair conformation, a side-by-side-pair conformation, and a parallel-pair conformation. QZ with the parallel-pair conformation and the minimum crystal cell volume exhibited a higher activity and a lower resistant level. XHR possessed a higher content of TCA cycle metabolites and phosphate than YJS, but the exposure to QZ significantly reduced the contents of citrate, isocitrate, alpha-ketoglutarate and oxaloacetate in XHR, as did the exposure to other technical tebuconazoles. Moreover, the point mutations F487L, G464S, and G443S altered the binding properties of chiral stereoscopic R-QZ with CYP51 protein. Especially the G443S mutation promoted a weak linking of R-QZ with LEU380 and TYR126, and greatly slashed the binding action at lower docking score. In con-clusion, our results evidenced an efficient crystal conformation of tebuconazole to improve botryticidal activity and a potential adaptability of B. cinerea to tebuconazole inhibition in TCA cycle metabolism and CYP51 protein mutation.