探索在Actinomycetes中发现天然产品的一般多方激活策略
Dillon W P Tay1, Lee Ling Tan2, Elena Heng2
1Institute of Sustainability for Chemicals, Energy and Environment (ISCE2), Agency for Science, Technology and Research (A*STAR), 8 Biomedical Grove, #07-01 Neuros Building, Singapore, 138665, Republic of Singapore.
Communications biology
|January 6, 2024
概括
研究人员开发了一种新方法来激活细菌中的抗生素生产,大大扩大了天然产品的范围和产量. 这种方法释放了大自然对药物发现的化学潜力.
科学领域:
- 微生物学 微生物学
- 自然产品化学 自然产品化学
- 生物信息学是一种生物信息学.
背景情况:
- 自然产品具有巨大的治疗前景,但由于生产和发现的挑战,它们在很大程度上未被开发.
- 现有的激活自然产品生物合成的方法对于各种微生物集合的范围和效率有限.
研究的目的:
- 开发一个全面和可扩展的战略,以获得天然产品生物合成.
- 创建一种可通用的方法,用于询问各种原生微生物菌株,以发现新型化合物.
主要方法:
- 实施了整合酶介导的多端激活方法,以全球触发抗生素生产.
- 在54种actinobacterial菌株中应用了该方法,产生了124种激活剂-菌株组合.
主要成果:
- 新型激活方法的表现始终优于野生型菌株.
- 可访问的代谢物空间扩大了近两倍,精选的代谢物产量增加了200倍以上.
- 能够发现具有格拉姆阴性生物活性的新型四酸类似物.
结论:
- 开发的激活策略提供了一个简化,加速和可扩展的途径,以利用自然产品的化学多样性.
- 这种方法代表了在释放微生物化学谱的全部潜力,以治疗应用的重大进步.
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