Liu Xiuyu, Ma Ying, Bu Junling, Lian Conglong, Ma Rui, Li Qishuang, Jiao Xiang, Hu Zhimin, Chen Yun, Chen Suiqing, Guo Juan, Huang Luqi
School of Pharmaceutical Sciences, Henan University of Chinese Medicine, No. 156 Jinshuidong Road, Zhengzhou, 450046, China.
State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, National Resource Center for Chinese Materia Medica, Chinan Academy of Chinese Medical Sciences, Beijing, 100000, China.
Plant Mol Biol. 2024 Mar 7;114(2):23. doi: 10.1007/s11103-023-01397-7.
Benzylisoquinoline alkaloids (BIAs) represent a significant class of secondary metabolites with crucial roles in plant physiology and substantial potential for clinical applications. CYP82 genes are involved in the formation and modification of various BIA skeletons, contributing to the structural diversity of compounds. In this study, Corydalis yanhusuo, a traditional Chinese medicine rich in BIAs, was investigated to identify the catalytic function of CYP82s during BIA formation. Specifically, 20 CyCYP82-encoding genes were cloned, and their functions were identified in vitro. Ten of these CyCYP82s were observed to catalyze hydroxylation, leading to the formation of protopine and benzophenanthridine scaffolds. Furthermore, the correlation between BIA accumulation and the expression of CyCYP82s in different tissues of C. yanhusuo was assessed their. The identification and characterization of CyCYP82s provide novel genetic elements that can advance the synthetic biology of BIA compounds such as protopine and benzophenanthridine, and offer insights into the biosynthesis of BIAs with diverse structures in C. yanhusuo.
苄基异喹啉生物碱（BIAs）是一类重要的次生代谢产物，在植物生理中发挥着关键作用，并且在临床应用方面具有巨大潜力。CYP82基因参与多种BIA骨架的形成和修饰，促进了化合物的结构多样性。在本研究中，对富含BIAs的传统中药延胡索进行了研究，以确定CYP82s在BIA形成过程中的催化功能。具体而言，克隆了20个编码CyCYP82的基因，并在体外鉴定了它们的功能。观察到其中10个CyCYP82s催化羟基化反应，导致原阿片碱和苯并菲啶骨架的形成。此外，还评估了延胡索不同组织中BIA积累与CyCYP82s表达之间的相关性。CyCYP82s的鉴定和表征提供了新的遗传元件，可推动原阿片碱和苯并菲啶等BIA化合物的合成生物学发展，并为延胡索中具有不同结构的BIAs的生物合成提供见解。
