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Metab Engin:人参皂苷细胞工厂构建方面取得新进展

  1. 人参皂苷
  2. 新进展
  3. 细胞工厂构建

来源:天津工业生物技术研究所 2013-11-21 19:13

人参皂苷(Ginsenosides)是名贵中药材人参(Panax ginseng)的主要活性成分。

人参皂苷(Ginsenosides)是名贵中药材人参(Panax ginseng)的主要活性成分。原人参二醇(protopanaxadiol)作为人参二醇型人参皂苷的苷元,其本身具有抗癌、抗抑郁、激活氯离子通道和抑制钠离子通道去极化的作用、抑制人胚肾HEK-293细胞和幽门螺旋杆菌生长等多种药理活性。其糖基化产物如人参皂苷Rh2、人参皂苷Rg3等在心脑血管治疗和抗肿瘤等方面有很好的药理活性,这类化合物的相关产品已在临床广泛使用。

中科院天津工业生物技术研究所张学礼研究员课题组与中国中医科学院中药资源中心黄璐琦研究员课题组合作,在酿酒酵母中成功构建原人参二醇的生物合成途径(图1),并且发现鲨烯环氧酶在控制三萜化合物的生物合成中起关键作用。在此基础上,通过提高3-羟基-3-甲基戊二酰辅酶A还原酶、法呢烯焦磷酸合酶、鲨烯合成酶和鲨烯环氧酶的活性,将原人参二醇的产量提高了262倍。通过双相发酵工艺优化,最终将原人参二醇的产量提高至1189mg/L。该研究为人参皂苷生物合成途径解析和异源生物合成提供了坚实的基础。

该研究得到国家“973”、“863”项目和自然科学基金的支持,相关研究成果已经发表在Metabolic Engineering期刊。天津工业生物所的戴住波博士和天津科技大学的联合培养研究生刘怡为论文的共同第一作者。(生物谷Bioon.com)

生物谷推荐的英文摘要

Metabolic Engineering          doi.org/10.1016/j.ymben.2013.10.004

Metabolic engineering of Saccharomyces cerevisiae for production of ginsenosides

Zhubo Daia, b, 1, Yi Liua, b, c, 1, Xianan Zhangd, e, Mingyu Shia, b, c, Beibei Wanga, b, c, Dong Wanga, b, c, Luqi Huangd,Xueli Zhanga, b

Ginsenosides are the primary bioactive components of ginseng, which is a popular medicinal herb and exhibits diverse pharmacological activities. Protopanaxadiol is the aglycon of several dammarane-type ginsenosides, which also has anticancer activity. For microbial production of protopanaxadiol, dammarenediol-II synthase and protopanaxadiol synthase genes of Panax ginseng, together with a NADPH-cytochrome P450 reductase gene of Arabidopsis thaliana, were introduced into Saccharomyces cerevisiae, resulting in production of 0.05 mg/g DCW protopanaxadiol. Increasing squalene and 2,3-oxidosqualene supplies through overexpressing truncated 3-hydroxyl-3-methylglutaryl-CoA reductase, farnesyl diphosphate synthase, squalene synthase and 2,3-oxidosqualene synthase genes, together with increasing protopanaxadiol synthase activity through codon optimization, led to 262-fold increase of protopanaxadiol production. Finally, using two-phase extractive fermentation resulted in production of 8.40 mg/g DCW protopanaxadiol (1189 mg/L), together with 10.94 mg/g DCW dammarenediol-II (1548 mg/L). The yeast strains engineered in this work can serve as the basis for creating an alternative way for production of ginsenosides in place of extraction from plant sources.

 

 

 

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