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有机化学
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有机化学 ›› 2014, Vol. 34 ›› Issue (7): 1376-1381.DOI: 10.6023/cjoc201403032 上一篇    下一篇

研究论文

基于生物合成途径改造的一个三欣卡辛类似物的发现

漆丽华a, 张媚b, 潘海学b, 陈晓东a, 唐功利b   

  1. a 江西中医药大学药学院 南昌 330004;
    b 中国科学院上海有机化学研究所 生命有机化学国家重点实验室 上海 200032
  • 收稿日期:2014-03-13 修回日期:2014-03-24 发布日期:2014-04-02
  • 通讯作者: 唐功利 E-mail:apple_chen_xd@163.com;gltang@sioc.ac.cn
  • 基金资助:

    国家自然科学基金（No.81202442）资助项目.

Production of a Trioxacarcin Analogue by Engineering of Its Biosynthetic Pathway

Qi Li-Huaa, Zhang Meib, Pan Hai-Xueb, Chen Xiao-Donga, Tang Gong-Lib   

  1. a College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004;
    b State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032
  • Received:2014-03-13 Revised:2014-03-24 Published:2014-04-02
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No. 81202442).

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三欣卡辛是一种来源于链霉菌的具有良好抗肿瘤活性的芳香聚酮类天然产物. 我们通过对三欣卡辛的发酵和分离条件进行优化，显著地提高了其产量. 通过对基因簇中一个酰基转移酶（Trx49）编码基因的敲除，改动了三欣卡辛的生物合成途径，获得了C-4位糖基上O-乙酰基缺失的三欣卡辛类似物1. 体外细胞毒性测试考察糖基上的O-乙酰基修饰缺失对三欣卡辛的影响，发现化合物1的生物活性比三欣卡辛A有所降低，但仍具有IC50为4.86 nmol·L-1的优异抗肿瘤细胞活性.

关键词: 三欣卡辛, 生物合成, 天然产物, 酰基转移酶

Trioxacarcins, derived from streptomyces, are aromatic polyketide natural products with antitumor activity. The production of trioxacarcins was improved significantly by optimizing the fermentation and purification processes. The biosynthetic pathway of trioxacarcins was changed by inactivating an acyltransferase (Trx49) gene in the trioxacarcin cluster, and an analogue compound 1 lacking the O-acetyl group of sugar on C-4 was obtained. The influence of the O-acetyl group on biological activity of trioxacarcins was investigated by in vitro cytotoxicity test. Compared with trioxacarcin A, the activity of compound 1 decreases to some extent but still persists an excellent anti-tumor activity level with IC50 value of 4.86 nmol·L-1.

Key words: trioxacarcin, biosynthesis, natural product, acyltransferase