控制真菌多基生物合成中的化学模块化的生化和结构基础
Jaclyn M Winter1, Duilio Cascio2, David Dietrich3
1†Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, California 90095, United States.
Journal of the American Chemical Society
|July 15, 2015
概括
代的真菌多基基合成酶 (IPKS) 使用起始单元乙烯载体蛋白转化酶 (SAT) 域进行结构多样化. 这项研究显示,
科学领域:
- 生物化学
- 分子生物学
- 自然产品生物合成
背景情况:
- 代真菌聚化酶 (IPKS) 之间的模块化协作产生了多样化的聚化天然产物.
- 接受IPKS模块中的PKS间通信和基质通道主要由启动单元乙载体蛋白转化酶 (SAT) 域进行调节.
研究的目的:
- 复制 chaetoviridin 和 chaetomugilin azaphilone 天然产品的甲基核心的模块化生物合成.
- 阐明CazM SAT域在CazF选择性基质转移中的作用.
- 通过真菌SAT域来确定乙基单元选择性的结构基础.
主要方法:
- 使用IPKS CazF和CazM进行模块化生物合成的复制.
- 生物化学测试以评估基质转移和SAT域的识别.
- 用X射线结晶学测定真菌SAT域的结构,包括活性位点中间体.
主要成果:
- CazM SAT域选择性地从CazF转移了一个减少的三化物产品.
- 由CazF产生的一种更加氧化的三化物,不被CazM SAT域识别.
- 一个真菌SAT域的第一个X射线结构揭示了共价六乙中间体,解释了单元的选择性.
结论:
- 在阿扎菲隆生物合成过程中,CazM SAT域在控制基质流量方面发挥着关键作用.
- 对真菌SAT域功能的结构见解为蛋白质工程提供了基础.
- 这项工作可以设计用于新天然产品生物合成的新型IPKS组合.
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