在家养的,生产PladienolideStreptomyces的细菌的比较基因组学和代谢学
Barbara I Adaikpoh1,2, Taylor Kornfuehrer1,2, Yitao Dai1,2
1Department of Pharmaceutical Sciences, Retzky College of Pharmacy, University of Illinois Chicago, Chicago, Illinois 60601, United States.
Journal of natural products
|March 10, 2026
概括
细菌的实验室化影响了天然产品的产量. 这项研究发现白色的Streptomyces platensis分离物具有3倍高的Pladienolide B产量,为抗生素开发提供了洞察力.
科学领域:
- 微生物学 微生物学
- 自然产品化学 自然产品化学
- 基因组学就是基因组学.
背景情况:
- 实验室培养细菌可以减少天然产品的合成.
- 来自Streptomyces platensis的Pladienolides是有前途的抗癌药物,在急性髓性白血病的临床试验中有合成衍生物.
研究的目的:
- 在Streptomyces platensis培养物中调查表型异质性.
- 识别影响化生产的因素.
- 描述与改善代谢物产量相关的遗传变异.
主要方法:
- 在Streptomyces platensis Mer-11107.7.的培养中使用.
- 16S rRNA基因测序用于物种识别.
- 代谢物分析 (HPLC).
- 实验性的进化.
- 进行比较的基因组学.
主要成果:
- 同样的16S rRNA基因序列证实黑色,灰色和白色殖民地属于同一物种.
- 一个白色分离物显示了Pladienolide B标位的3倍增加.
- 实验进化表明,黑色分离物可以产生灰色和白色变体,但不能反过来,这表明不可逆转的变化.
- 比较基因组学确定了序列和结构变异,可能解释表型差异.
结论:
- 由基因组不稳定性驱动的Streptomyces殖民地中的表型异质性,可以导致特殊的细胞功能,如增强抗生素生产.
- 确定了Pladienolide B的过度生产者,这有助于进一步研究拼接调节性抗瘤剂.
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