Zhang Yuhua, Jiang Jiayi, Qin Ningbo, Zhang Qian, Yan Chunyan
School of Pharmacy, Guangdong Pharmaceutical University Guangzhou 510006 China
RSC Adv. 2019 Mar 25;9(17):9449-9456. doi: 10.1039/c9ra00522f. eCollection 2019 Mar 22.
Cambial meristematic cell (CMC) suspension cultures were investigated as a new biotransformation system for the first time. Four 4-methylcoumarins substrates were transformed by CMCs of into four corresponding products, including 4,8-dimethylcoumarin-7--β-d-glucopyranoside (I-1), 4,7-dimethylcoumarin-6--β-d-glucopyranoside (II-1), 6-hydroxy-7-methoxyl-4- methylcoumarin (III-1), and 4,7-dimethylcoumarin-5--β-d-glucopyranoside (IV-1), of which I-1, II-1, and IV-1 were new compounds. In addition, the biotransformation time and the amount of substrate were investigated to compare the biotransformation rate and optimize the biotransformation conditions of the four substrates in CMCs suspension cultures. The results suggested CMCs were able to select glycosylate phenolic hydroxyl groups of 4-methylcoumarins I, II, and IV, with high regio- and stereoselectivity, but no corresponding glycoside of any phenolic hydroxyl group of compound III was detected. Simultaneously, the result also showed that the CMCs were able to transform the 7-hydroxy groups of substrate III to its corresponding methylated products. Furthermore, the monoamine oxidase (MAO) inhibition activities of biotransformed products were evaluated, and the data showed that all the products possessed good MAO inhibition activities . In conclusion, CMCs could be applied to glycosylation biotransformation as a novel plant-based system due to the successful application of bioconversion of exogenous coumarins.
首次将形成层分生组织细胞(CMC)悬浮培养物作为一种新的生物转化系统进行研究。四种4-甲基香豆素底物被CMC转化为四种相应产物,包括4,8-二甲基香豆素-7--β-d-吡喃葡萄糖苷(I-1)、4,7-二甲基香豆素-6--β-d-吡喃葡萄糖苷(II-1)、6-羟基-7-甲氧基-4-甲基香豆素(III-1)和4,7-二甲基香豆素-5--β-d-吡喃葡萄糖苷(IV-1),其中I-1、II-1和IV-1为新化合物。此外,研究了生物转化时间和底物量,以比较四种底物在CMC悬浮培养物中的生物转化率并优化生物转化条件。结果表明,CMC能够以高区域选择性和立体选择性选择糖基化4-甲基香豆素I、II和IV的酚羟基,但未检测到化合物III任何酚羟基的相应糖苷。同时,结果还表明,CMC能够将底物III的7-羟基转化为其相应的甲基化产物。此外,评估了生物转化产物的单胺氧化酶(MAO)抑制活性,数据表明所有产物均具有良好的MAO抑制活性。总之,由于外源香豆素生物转化的成功应用,CMC可作为一种新型的基于植物的系统应用于糖基化生物转化。