用于生物合成含硫环的酶环收缩
Qiuyue Nie1,2,3, Chunxiao Sun1,2,3, Shuai Liu1,2,3
1Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, Pennsylvania19104, United States.
Journal of the American Chemical Society
|December 16, 2024
概括
研究人员发现了一种新酶IscL, 这种酶
科学领域:
- 生物化学
- 自然产品生物合成
- 酵素学
背景情况:
- 环染色体是许多生物活性天然产品中的关键结构图案.
- 环染色体的生物合成途径和酶的起源在很大程度上仍然难以捉摸.
- 已经确定了一种新型的环色素衍生物,即具有碳-硫键的同染色硫.
研究的目的:
- 阐明导致环染色体支架形成的酶机制.
- 鉴定催化键环收缩过程中的酶.
- 研究已识别的酶在修改桑前体中的催化灵活性.
主要方法:
- 一种依赖FAD的单氧酶的识别和特征,称为IscL.
- 使用xanthon前体进行酶分析以研究2S-remisporine A的形成.
- IscL的位点定向突变,以探测关键残留物在催化结果 (环收缩与裂变) 的作用.
主要成果:
- 通过环收缩,IscL从一个6/6/6的xanone前体中催化形成2S-remisporine A.
- 反应性中间体2S-雷米斯波林A经过自发的醇-迈克尔添加,形成异染色硫.
- IscL同类物表现出分叉活性,导致Xanthone中间体的环收缩或环裂变,由230位的关键残留物调节.
结论:
- 在建立6/6/5环染色体核心结构方面,FAD依赖的单氧酶IscL起着关键作用.
- 该研究揭示了IscL的催化机制,包括其调解环收缩的能力和基质特异性.
- 这些发现为含有环染色体的天然产品的基因组挖掘提供了基础,并突出了IscL在生物催化中的潜力.
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