Two types of coumarins-specific enzymes complete the last missing steps in pyran- and furanocoumarins biosynthesis

作     者：Yucheng Zhao Yuedong He Liangliang Han Libo Zhang Yuanzheng Xia Fucheng Yin Xiaobing Wang Deqing Zhao Sheng Xu Fei Qiao Yibei Xiao Lingyi Kong 

作者机构：Department of Resources Science of Traditional Chinese MedicinesSchool of Traditional Chinese Pharmacyand State Key Laboratory of Natural MedicinesChina Pharmaceutical UniversityNanjing 210009China College of Bioscience and BiotechnologyHunan Agricultural UniversityChangsha 410128China Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural MedicinesDepartment of Natural Medicinal ChemistryChina Pharmaceutical UniversityNanjing 210009China Key Laboratory of Crop Gene Resources and Germplasm Enhancement in Southern ChinaMinistry of AgricultureTropical Crops Genetic Resources InstituteChinese Academy of Tropical Agricultural SciencesHaikou 517317China Institute of BotanyJiangsu Province and Chinese Academy of SciencesNanjing 210014China Department of PharmacologySchool of Pharmacyand State Key Laboratory of Natural MedicinesChina Pharmaceutical UniversityNanjing 210009China 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2024年第14卷第2期

页      面：869-880页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 100701[医学-药物化学] 10[医学] 

基　　金：National Key Research and Development Program of China (2018YFA0902000) the key project at central government level:the ability establishment of sustainable use for valuable Chinese medicine resources(2060302,China) the open foundation of Shaanxi University of Chinese Medicine state key laboratory of R&D of Characteristic Qin Medicine Resources (SUCM-QM202202,China) the fund of Traditional Chinese Medicine Institute of Anhui Dabie Mountain (TCMADM-2023-18,China) National Natural Science Foundation of China (32070364) Hainan Provincial Natural Science Foundation of China(2019RC309) 

主　　题：Tetrahydropyrans Tetrahydrofurans Baldwin rules Coumarins CYP450cyclase 

摘      要：Pyran-and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans,respectively,exhibiting diverse physiological and medical ***,the biosynthetic mechanisms for their core structures remain poorly *** we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in *** included three distinct *** prenyltransferases(PpPT1e3)responsible for the prenylation of the simple coumarin skeleton 7 into linear or angular precursors,and two novel CYP450 cyclases(PpDC and PpOC)crucial for the cyclization of the linear/angular precursors into either tetrahydropyran or tetrahydrofuran *** analyses of cyclases indicated that acid/base-assisted epoxide ring opening contributed to the enzyme-catalyzed tetrahydropyran and tetrahydrofuran ring *** possible acid/base-assisted catalytic mechanisms of the identified cyclases were theoretically investigated and assessed using site-specific *** identified two possible acidic amino acids Glu303 in PpDC and Asp301 in PpOC as vital in the catalytic *** study provides new enzymatic tools in the epoxide formation/epoxide-opening mediated cascade reaction and exemplifies how plants become chemically diverse in terms of enzyme function and catalytic process.