通过异构表达来扩大灰的化学多样性
Wei Liu1,2, Shilan Zhai1,3, Liping Zhang1,3
1Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, People's Republic of China.
Journal of natural products
|February 1, 2024
概括
研究人员从Streptomyces中发现了新的 thiazole 化合物,包括具有独特的酸组的 grisechelin F. 一种化合物显示出对Mycobacterium tuberculosis的抗菌活性.
科学领域:
- 自然产品化学 自然产品化学
- 微生物生物合成
- 药物发现 药物发现
背景情况:
- 含有 thiazole 的小分子由于其多样化的生物活动,在药物发现中至关重要.
- 杆菌 (Streptomyces) 种类是生物活性天然产品的丰富来源.
研究的目的:
- 识别和描述Streptomyces sp.中含有 thiazole 的新型化合物. 在SCSIO 40020上.
- 为了研究一种独特的 thiazole 衍生物的生物合成途径.
主要方法:
- 生物信息学分析以确定一个假定的生物合成基因集群 (BGC).
- BGC的异质表达产生新型化合物.
- 使用HRESIMS,NMR,ECD计算和X射线结晶学阐明结构.
- 基因淘汰实验用于研究生物合成途径.
主要成果:
- 生产了八种新的 thiazole 化合物 (灰素 E,F,I-N) 和两种素衍生物 (灰素 G,H).
- 确定了化合物1-10的结构和绝对配置.
- 格里舍林F (2) 被确定为一种独特的衍生品,含有酸部分.
- 格里舍林E (1) 对Mycobacterium tuberculosis H37Ra (MIC = 8μg mL−1) 具有中度的抗菌活性.
结论:
- 该研究成功地识别和表征了Streptomyces的新型 thiazole 和 quinoline 衍生物.
- 提出了一个独特的 thiazole 衍生物的生物合成途径.
- 这些发现有助于了解微生物天然产品生物合成,并为抗菌细菌药物发现提供潜在的线索.
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