通过先基因替代和Bacillus cereus的体内加工生成硫素环大小变异
Albert A Bowers1, Michael G Acker, Travis S Young
1Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana 47907, USA.
Journal of the American Chemical Society
|June 13, 2012
概括
谷菌种可以产生硫素,天然的 thiazolyl . 竞争实验揭示了关键的循环化步骤可以创造新的,多样化的环形大小,扩大自然产品的多样性.
科学领域:
- 自然产品生物合成 自然产品生物合成
- 微生物的二次代谢
- 化学生物学 化学生物学
背景情况:
- 提奥西林是Bacillus cereus产生的 thiazolyl 类.
- 生物合成涉及前体的翻译后修改.
- 一个关键的步骤是两个氨酸残留物之间的正式循环加法,形成一个宏循环.
研究的目的:
- 为了研究西林生物合成中最后的宏循环化步骤的乱交性.
- 通过改变循环化来探索变种环形大小的生成.
- 为了扩大已知的自然 thiazolyl 的结构多样性.
主要方法:
- 利用竞争实验来探测循环化反应.
- 分析产品以识别和表征变异的环结构.
- 采用遗传或生物化学方法来研究Bacillus cereusATCC 14579生物合成.
主要成果:
- 在宏观循环化步骤中表现出显著的乱交.
- 成功生成并识别了几种具有改变环形大小的硫素变体.
- 观察到的环形大小以前在天然硫素中没有报告过.
结论:
- 西林生物合成中的最后一个宏循环化步骤非常灵活.
- 这种灵活性允许自然生成多种类型的 thiazolyl 结构.
- 这些发现为发现具有独特环形结构的新型自然产品开辟了道路.
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