在sorbicillinoid生物合成中涉及的Flavin依赖单氧化酶和氧化酶的结构和机制特征
Gwen Tjallinks1,2, Nicolò Angeleri1, Quoc-Thai Nguyen3
1Department of Biology and Biotechnology, University of Pavia, Via Adolfo Ferrata 9, Pavia 27100, Italy.
ACS chemical biology
|March 7, 2025
概括
对SorC和Sord酶的结构洞察力揭示了生产多种菌类物的一类黄色真菌代谢物的关键机制. 了解这些依赖黄素的酶有助于探索复杂的生化途径.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 菌类学 菌类学是指菌类学.
背景情况:
- 皮类化合物是菌通过复杂的生物化学途径产生的黄色二次代谢物.
- 黄素依赖的酶,特别是SorC (单氧化酶) 和SorD (氧化酶),在类类生物合成中起着关键作用.
- 阐明这些酶的结构和功能对于理解各种基类化合物的生成至关重要.
研究的目的:
- 为了确定SorC和SorD的晶体结构,从与sorbicillin结合的Penicillium chrysogenum中获得.
- 描述SorC和Sord的催化活性结合形态.
- 研究关键残留物和辅因子相互作用在SorC和Sord的酶活性中的作用.
主要方法:
- 使用X射线晶体学,用素解决了SorC和Sord的结构.
- 用定位突变和生物化学表征来研究SorC变体.
- 基于CRISPR/Cas9的多复制基因组集成被用于SORD在*Aspergillus niger*中的异质表达.
主要成果:
- 确定了SorC和Sord的晶体结构,在活性位点结合索比西林,揭示了对enantioselective和stereoselective控制的关键构造.
- 在"外"状态下使用flavin-adenine dinucleotide (FAD) 的SorC结构确定了调节flavin流动性的关键残留物.
- SorD 的高产异质表达使其催化 conformation 和基质结合 pose 的结构分析成为可能.
结论:
- 已确定的结构为sorbicillinoid生物合成中的SorC和SorD的机制提供了原子层面的见解.
- 了解SorC和SorD之间的相互作用是解读广泛的功能复杂sorbicillinoids的生产的关键.
- 这项研究为进一步研究控制真菌二次代谢物生产的酶机制奠定了基础.
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