生物合成编程的结构基础是真菌芳香聚基酸循环的生物合成编程
Jason M Crawford1, Tyler P Korman, Jason W Labonte
1Department of Chemistry, Johns Hopkins University, Maryland 21218, USA.
Nature
|October 23, 2009
概括
研究人员阐明了真菌聚基化物合成中的关键酶域的结构和功能. 这项工作揭示了这些酶如何控制复杂分子的产生,如阿弗拉托克辛B1.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 自然产品的合成自然产品的合成
背景情况:
- 聚基类是具有多种结构和生物活性的天然产品.
- 的代多基合成酶 (IPKSs) 通过复杂的循环生成芳香化合物.
- 控制聚基化循环化特异性的机制在很大程度上仍然未知.
研究的目的:
- 确定NR-PKSs.中的产品模板 (PT) 域的结构和机制.
- 了解PT域如何控制多基化循环和芳香化.
- 提供关于阿弗拉托克辛B1.1生物合成的见解.
主要方法:
- 来自PksA.的切割PT单主体的X射线晶体学.
- 与基质模仿物 (棕酸盐,双循环模拟物) 共同结晶.
- 现场定向的突变发生和分子对接研究.
主要成果:
- 在PT域采用了新的"双热狗" (DHD) 折叠.
- PT 结合了线性和双循环的多基胺前体.
- 确定了基质结合,催化和独特的结合口袋的关键残留物.
结论:
- 在IPKS中,DHD折叠和PT域的活性位点被保留.
- 对PT功能的机械洞察力可用于NR-PKS循环控制.
- 这项研究为理解和工程NR-PKS特异性奠定了基础.
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