基于祖先序列重建的醇氧化细胞染色体P450酶选择性的进化见解
Daniel Z Doherty1, James J De Voss2, John B Bruning3
1Department of Chemistry, University of Adelaide Adelaide South Australia 5005 Australia daniel.z.doherty@adelaide.edu.au stephen.bell@adelaide.edu.au.
Chemical science
|May 26, 2025
概括
祖先序列重建显示,古老的细胞染色体P450 (CYP) 酶CYP125MRCA进化了扩大的基质范围,包括维生素D3. 这种适应可能反映了其向菌根菌中的病原性利基的演变.
科学领域:
- 生物化学 生物化学
- 进化生物学 进化生物学
- 微生物学 微生物学
背景情况:
- 细胞染色体P450 (CYP) 酶,特别是CYP125A1,对于Mycobacterium tuberculosis的生存和致病性至关重要.
- 在Actinobacteria中,CYP125基因广泛存在,通常有多个副本,主要是基酸醇.
研究的目的:
- 调查CYP125酶中基质选择性的进化起源.
- 为了测试CYP125酶进化以适应病原性的假设.
主要方法:
- 祖先序列重建 (ASR) 用于确定CYP125基团 (CYP125MRCA) 最新的共同祖先.
- 重建的CYP125MRCA酶的功能和结构特征.
- 结合醇和维生素D的CYP125MRCA的X射线晶体学3.
主要成果:
- CYP125MRCA催化胆固醇,植物和维生素D3的终端氧化.
- 维生素D3通过CYP125MRCA在C-25和C-26两种氧化,这是该酶家族的一种新活动.
- 结构分析提供了对CYP125MRCA扩大基质范围的分子基础的见解.
结论:
- 重建的祖先CYP125MRCA酶表现出比其现存的亲属更广泛的基质范围.
- ASR提供了与致病性生活方式相关的CYP125酶适应性演变的证据.
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