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细菌生物合成和成熟的dedemnin抗癌药物
Ying Xu1, Roland D Kersten, Sang-Jip Nam
1KAUST Global Collaborative Research, Division of Life Science, School of Science, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Journal of the American Chemical Society
|March 31, 2012
概括
海洋鱼产生的抗癌化合物,但供应有限. 这些恶魔实际上是由细菌制造的,为药物生产和开发提供了新的途径.
科学领域:
- 海洋天然产品 海洋天然产品
- 细菌生物合成的细菌生物合成
- 药物发现 药物发现
背景情况:
- 迪德明尼B是一种来自Trididemnum solidum的海洋天然产品,是人类临床试验中的第一个海洋药物.
- 迪德姆宁的供应有限和复杂结构阻碍了药物开发,影响了阿普利丁 (脱二丁B) 的临床试验.
研究的目的:
- 为了识别dedemnins的来源并阐明它们的生物合成途径.
- 为了解决基于迪德姆宁的抗癌剂的供应限制.
主要方法:
- 在Tistrella mobilis的全基因组测序.
- 对假设的迪德姆宁生物合成基因集群 (did) 的分析.
- 用成像质谱测量来观察前体转化.
主要成果:
- 迪德明是由海洋α-蛋白质细菌Tistrella mobilis和Tistrella bauzanensis合成的细菌产物.
- 迪德姆宁生物合成基因集群 (did) 在T. mobilis中的一个大质粒上被确定.
- 迪德明因X和Y首先被合成,然后通过一种新的后组装机制在细胞外转化为迪德明因B.
结论:
- 迪德明的细菌起源解决了这些海洋天然产品的供应问题.
- 发现方便了基因工程的新奇的丁类似物.
- 这一发现为开发基于迪德姆宁的治疗方法开辟了新的途径.
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