通过对非正规IB类合成酶的基因组挖掘,扩大四分之一的结构多样性

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Shogo Iwakata¹, Ikiru Otsuka¹, Shuya Azuma¹

¹Department of Life and Food Sciences, Graduate School of Science and Technology, Niigata University, Ikarashi 2-8050, Nishi-ku, Niigata 950-2181, Japan.

ACS chemical biology

|December 22, 2025

概括

研究人员探索了细菌的烯合成酶 (IB-TPSs),以发现新的六四烯 (C35烯). 他们发现了新的循环化合物,扩大了这些罕见的自然产品已知的结构多样性.

科学领域:

自然产品化学自然产品化学
酶学是一种酶学.
基因组学就是基因组学.

背景情况:

四分之一 (C35) 是一种罕见的自然产物,已知结构有限.
非正规IB类合成酶 (IB-TPSs) 是唯一能够循环C35基质的已知酶.
尽管数据库中有许多细菌IB-TPS同类物质,但此前仅有两种四分之一被确定为它们的产物.

研究的目的:

探索细菌IB-TPS同类的生物合成潜力,以发现新的四分六烯.
调查IB-TPS序列标识与产品多样性之间的关系.

主要方法:

来自各种细菌物种的11个IB-TPS基因的基因挖掘.
在 * Bacillus subtilis * 中,IB-TPS 基因的异质表达.
使用振动圆形二重体和特定光学旋转进行产品分析.

主要成果:

在11种IB-TPS同类中的8种,与* Bacillus subtilis* TPS (BsuTPS) 相同度≥30%,产生了已知的四分六烯四烯-β-黄素.
测定了四烯-β-黄素的绝对立体化学是 (-) - 7R.
三种IB-TPS同类物,与BsuTPS相同度<30%,产生了三种新型周期性四分之一笔,其中一种具有独特的5/3融合式双循环骨架.

结论:

与已知的酶具有较低序列相同性 (<30%) 的IB-TPS同类物是发现结构新四分之一的有希望的来源.
这项研究显著扩大了已知的四分之一的结构多样性.
这种新型的四分之一可能来自于与以前描述的路径不同的碳化灭机制.

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