日本大阪大学的一个研究小组发现了中药中经常使用的一种植物甘草制造药学成分的遗传基因,并成功生产了甘草的药学成分。
甘草的药学成分具有增强肝脏机能以及抗炎症等作用,也是各种中药的“药引子”。在日本,除了医药品之外,在210种中药处方中约70%具有甘草成分配方。中国等国家主要依靠野生甘草。
研究小组发现,有两个遗传基因参与了合成甘草的医药成分甘草次酸。他们把这个遗传基因与同是豆科植物的莲花中抽取的酶组合,成功生产出了甘草次酸。研究负责人中村俊哉教授认为,该研究可能应用于工业生产甘草药用成分。他们计划今后提高生产量,同时还将对大豆等其他植物进行实验,研究应用的可行性。
研究成果发表于11月29日出版的美国科学杂志《植物细胞》电子版。(生物谷Bioon.com)
doi:10.1105/tpc.110.082685
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Triterpene Functional Genomics in Licorice for Identification of CYP72A154 Involved in the Biosynthesis of Glycyrrhizin
Hikaru Sekia, Satoru Sawaic, Kiyoshi Ohyamac, Masaharu Mizutanig, Toshiyuki Ohnishig, Hiroshi Sudod, Ery Odette Fukushimab, Tomoyoshi Akashih, Toshio Aokih,Kazuki Saitoc and Toshiya Muranakaa
Glycyrrhizin, a triterpenoid saponin derived from the underground parts of Glycyrrhiza plants (licorice), has several pharmacological activities and is also used worldwide as a natural sweetener. The biosynthesis of glycyrrhizin involves the initial cyclization of 2,3-oxidosqualene to the triterpene skeleton β-amyrin, followed by a series of oxidative reactions at positions C-11 and C-30, and glycosyl transfers to the C-3 hydroxyl group. We previously reported the identification of a cytochrome P450 monooxygenase (P450) gene encoding β-amyrin 11-oxidase (CYP88D6) as the initial P450 gene in glycyrrhizin biosynthesis. In this study, a second relevant P450 (CYP72A154) was identified and shown to be responsible for C-30 oxidation in the glycyrrhizin pathway. CYP72A154 expressed in an engineered yeast strain that endogenously produces 11-oxo-β-amyrin (a possible biosynthetic intermediate between β-amyrin and glycyrrhizin) catalyzed three sequential oxidation steps at C-30 of 11-oxo-β-amyrin supplied in situ to produce glycyrrhetinic acid, a glycyrrhizin aglycone. Furthermore, CYP72A63 of Medicago truncatula, which has high sequence similarity to CYP72A154, was able to catalyze C-30 oxidation of β-amyrin. These results reveal a function of CYP72A subfamily proteins as triterpene-oxidizing enzymes and provide a genetic tool for engineering the production of glycyrrhizin.