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通过区域特异性C-C键合,设计和生物合成二元性或黄素
Zhengyan Guo1, Pengwei Li1, Guozhu Chen2
1State Key Laboratory of Microbial Resources , Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101 , China.
Journal of the American Chemical Society
|December 6, 2018
概括
研究人员从Streptomyces alboflavus中设计了新型二元性阿尔博素 (di-AFNs). 与其单体对应物相比,这些二-AFN具有增强的抗菌和抗瘤特性,展示了天然产品药物发现的有希望的策略.
科学领域:
- 自然产品化学
- 合成生物学
- 微生物生物技术
背景情况:
- 阿尔博素 (AFN) 是来自Streptomyces alboflavus的循环,具有中度的抗菌和抗瘤活性.
- AFN生物合成涉及非核糖体合成酶机制,其中一个关键的6-chloro-L-tryptophan前体是由外部的基因提供.
- 类似AFN的化合物的结构-活性关系指导了新衍生物的设计.
研究的目的:
- 设计和产生具有区域特异性双链的二元性 alboflavusins (di-AFNs).
- 与单体形式相比,评估di-AFN增强的抗菌和抗瘤活性.
- 通过生物技术工程来改善自然产品的生物活性.
主要方法:
- 通过在Streptomyces alboflavus菌株 (野生型和突变型) 中表达P450基因 (hmtS或clpS) 来产生di-AFN.
- 基于相关环合的结构-活性关系知识的二-AFN的设计.
- 在体外和体内评估生成的二-AFN的抗菌和抗瘤活性.
主要成果:
- 成功设计和生成了两个具有区域特异性双链的二度AFN (di-AFN).
- 与其单体对应物相比,生成的二-AFN具有显著改善的抗菌和抗瘤活性.
- 这项研究证实了合理设计和生物技术方法提高天然产品疗效的有效性.
结论:
- 生物技术生产的di-AFN代表了一个成功的策略来产生新的天然产品同源.
- 经过工程设计的di-AFN显示出卓越的生物活性,为开发新的治疗药物提供了潜力.
- 这项工作是对天然产品药物发现和优化的合理方法的典范.
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