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P450 酶 LyoI 在聚乙烯离子中进行氧化

Michelle H Rasmussen¹, Søren L B Møller¹, Esben B Svenningsen¹

¹Department of Chemistry, Aarhus University, Langelandsgade 140, DK, Aarhus C, 8000, Denmark.

Angewandte Chemie (International ed. in English)

|September 2, 2025

概括

研究人员发现了一种新的酶,LyoI,负责聚乙烯离子体生物合成的独特氧化. 这种氧化对于素的抗菌作用至关重要,为酶的发现提供了新的途径.

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:

聚乙烯离子体具有强大的抗菌特性,但也具有哺乳动物细胞毒性.
聚乙烯离子体生物合成中的异常氧化转化在很大程度上仍未被探索.
某些聚乙烯离子体中的海米基特部分表明非正规的生物合成途径.

研究的目的:

在聚乙烯离子体生物合成中,识别出一种异常氧化转化的酶.
阐明这种氧化在多离子体的生物活性中的作用.
通过以生物合成为重点的方法探索新型酶的发现.

主要方法:

在S. longwoodensis中敲除CRISPR-BEST基因以确定负责的酶.
鉴定酶的体内功能复制 (LyoI).
在体外验证氧化反应和生物活性.
确定酶的序列相似性网络分析.

主要成果:

已确定P450酶LyoI负责-2,2'-双直接氧化为-2,2'-双-2-ol.
LyoI敲击产生了非氧化的前体,前素,使功能研究成为可能.
通过LyoI介导的氧化显著提高了聚乙烯离子体的生物效能.
确定了一种对LyoI氧化功能至关重要的酸性残留物.

结论:

这项研究提供了第一个lysocellin生物合成基因集群的注释,并将LyoI确定为一种新型氧化酶.
对于lysocellin的抗菌活性来说,lyoI介导的氧化是至关重要的.
这些发现突出了通过序列相似性网络和以生物合成为重点的策略识别非正规P450酶的潜力.

关键词:

生物活性生物合成化学酶合成自然产品酶P450的使用

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