日本大阪大學(xué)的一個研究小組發(fā)現(xiàn)了中藥中經(jīng)常使用的一種植物甘草制造藥學(xué)成分的遺傳基因,,并成功生產(chǎn)了甘草的藥學(xué)成分。
甘草的藥學(xué)成分具有增強(qiáng)肝臟機(jī)能以及抗炎癥等作用,,也是各種中藥的“藥引子”,。在日本,,除了醫(yī)藥品之外,在210種中藥處方中約70%具有甘草成分配方,。中國等國家主要依靠野生甘草。
研究小組發(fā)現(xiàn),,有兩個遺傳基因參與了合成甘草的醫(yī)藥成分甘草次酸,。他們把這個遺傳基因與同是豆科植物的蓮花中抽取的酶組合,成功生產(chǎn)出了甘草次酸,。研究負(fù)責(zé)人中村俊哉教授認(rèn)為,,該研究可能應(yīng)用于工業(yè)生產(chǎn)甘草藥用成分。他們計劃今后提高生產(chǎn)量,,同時還將對大豆等其他植物進(jìn)行實驗,,研究應(yīng)用的可行性。
研究成果發(fā)表于11月29日出版的美國科學(xué)雜志《植物細(xì)胞》電子版,。(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.