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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
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在素生物合成中形成螺旋的分子和计算基础
Xingxing Wei1, Taro Matsuyama2, Hajime Sato2,3
1Department of Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong SAR, China.
Journal of the American Chemical Society
|October 13, 2021
概括
研究人员阐明了真菌梅罗类素的生物合成,揭示了新型细胞P450酶机制,用于形成螺旋. 这一发现揭示了生物活性天然产品的生产.
科学领域:
- 自然产品生物合成
- 菌类的二次代谢
- 酶催化
背景情况:
- 生物活性天然产品中含有3H2,其中包括抗真菌药物格里索富尔文.
- 塞托苏辛 (1) 是一种由独特的螺旋合的3H- furanon结构特征的真菌甲基.
- 自从它被分离出来以来,塞托苏的生物合成途径一直未被研究.
研究的目的:
- 在Aspergillus duricaulisCBS 481.65中识别素 (1) 的生物合成基因集群.
- 通过Aspergillus oryzae的异质表达来阐明素 (1) 的生物合成途径.
- 了解螺旋形成的反应机制.
主要方法:
- 鉴定素生物合成基因群.
- 在Aspergillus oryzae中异构的酶活性.
- 在体内和体外同位素结合实验.
- 理论上的计算.
- 在SETF酶的位点定向突变发生.
主要成果:
- 确定了素 (1) 的生物合成基因集群.
- 这种生物合成途径在Aspergillus oryzae中被复制.
- 发现细胞P450酶SetF对螺旋的合成至关重要.
- SetF 催化了环氧化和由质子化启动的重新排列.
- 突变检测发现Lys303是SetF中的潜在催化残留物.
结论:
- 这项研究阐明了真菌美罗类素的生物合成途径 (1).
- 发现了一种涉及细胞染色体P450酶SetF形成螺旋的新机制.
- 这项研究提供了复杂的自然产品和酶功能的生物合成见解.
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