复杂性的组合生成由 chaetoglobosin A 生物合成中的氧化还原酶
Kan'ichiro Ishiuchi1, Takehito Nakazawa, Fumitoshi Yagishita
1Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
Journal of the American Chemical Society
|April 25, 2013
概括
这项研究详细介绍了大热球蛋白A的完整生物合成,确定了关键的氧化还原酶和中间体. 了解Chaetomium globosum中的这些通路有助于发现天然产品.
科学领域:
- 生物化学 生物化学
- 自然产品生物合成 自然产品生物合成
- 酶学 是一种酶学.
背景情况:
- 氧化还原酶对于产生自然产品中的结构复杂性至关重要.
- 氨酸A是一种复杂的天然产品,通过混合途径生物合成.
- 热球蛋白家族包括具有不同氧化状态的类似物.
研究的目的:
- 为了阐明从proximetoglobosin I中获得chaetoglobosin A的完整生物合成途径.
- 为了确定负责每个氧化步骤的特定氧化还原酶.
- 为了确定chaetoglobosin A生物合成的立体化学过程和中间体.
主要方法:
- 使用的Chaetomium globosum菌株在氧化还原酶基因 (FAD依赖单氧化酶,细胞染色体P450s) 中缺失.
- 通过Saccharomyces cerevisiae中基因的异质表达进行了体内生物转化实验.
- 使用X射线晶体结构分析确定了五种已识别的中间体的绝对配置.
主要成果:
- 确定了五种新型类似物,作为proxeetoglobosin I到Chaetoglobosin A氧化过程中的中间物.
- 阐明了氧化步骤的完整序列和催化它们的酶.
- 揭示了氧化还原酶的杂乱性,导致路径网络和中间体的组合性形成.
结论:
- 这项研究成功地绘制了Chaetoglobosin A.的完整生物合成途径.
- 证明了特定的氧化还原酶及其在产生结构多样性的杂乱性中的关键作用.
- 提出的方法可以加速阐明其他真菌天然产品的生物合成途径.
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