在Streptomyces rapamycinicus中发现了基因组驱动的素
Manar Magdy Mahmoud Mohamed1, Zhijie Yang1, Kah Yean Lum1
1Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads 221, 2800 Kgs. Lyngby, Denmark.
Journal of natural products
|April 22, 2024
概括
研究人员发现了来自Streptomyces rapamycinicus发酵的新安萨米天然产品. 这些发现扩大了已知的安萨米的结构多样性,包括新型的二氧化-素化合物.
科学领域:
- 自然产品化学 自然产品化学
- 微生物生物技术 微生物生物技术
- 有机合成 有机合成
背景情况:
- 安萨米辛,以利法米辛为例,是具有重要的药物应用,特别是作为抗结核药物的重要自然产品类别.
- 对微生物二次代谢物的探索对于发现具有潜在治疗价值的新化学实体至关重要.
研究的目的:
- 从Streptomyces rapamycinicus中分离和表征新的安萨米辛类似物.
- 阐明安萨胺素的生物合成途径,特别是确定负责安萨环形成的酶.
主要方法:
- 在50升尺度上发酵Streptomyces rapamycinicus IMET 43975的发酵.
- 使用染色学技术净化安萨米化合物.
- 通过全面的光谱分析 (1D/2D NMR,ECD) 和质谱法 (MS) 阐明结构.
- 使用 in vivo CRISPR 基编辑证实了 Baeyer-Villiger 酶的作用.
主要成果:
- 隔离和识别了八种安萨米辛化合物,包括五种已知的和四种新的类似物.
- 作为一个佐基诺诺依德ansamycin.hygrocin W的表征.
- 发现了三种新的二氧化素化合物 (二氧化素X-Z).
- 确认一个特定的贝耶-维利格酶在安萨米生物合成中的功能.
结论:
- 该研究通过分离新型化合物成功扩大了安萨米辛的结构多样性.
- 鉴定新的安萨米辛和阐明生物合成机制为天然产品化学提供了宝贵的知识.
- 这项研究强调了微生物发酵在发现复杂自然产品方面的潜力.
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