在多基基生物合成中的O-甲基转移酶类酶催化二装置
Yuchun Zhao1, Xiangyang Liu1, Zhihong Xiao1
1State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 200030, Shanghai, P. R. China.
Nature communications
|September 4, 2023
概括
研究人员确定了AlpH,一种类似O-甲基转移酶的蛋白质,对于在罕见的金胺天然产品中形成二组至关重要. 这一发现阐明了生产强效化疗剂的关键步骤.
科学领域:
- 生物化学 生物化学
- 自然产品 化学 化学
- 合成生物学 合成生物学
背景情况:
- 酸化合物是罕见的自然产品,具有显著的生物活性,包括强大的化疗特性.
- 基纳米辛和洛马维维提辛,具有一个diazobenzofluorene核心,是这样的化合物的例子,但diazo组形成的机制是不太了解.
- 虽然L-glutamylhydrazine在胺酸生物合成中被称为胺酸供体,但其结合的具体酶化步骤仍然难以捉摸.
研究的目的:
- 阐明氨酸组在氨酸生物合成中的安装机制.
- 确定负责催化这些天然产品中子组的形成的酶.
- 扩大对聚基化生物合成中的酶反应的理解.
主要方法:
- 对类似O-甲基转移酶的蛋白质AlpH的生物化学表征.
- 使用聚基介质和L-glutamylhydrazine的酶测试来确定AlpH的催化活性.
- 对反应机制的分析,包括基质特异性和辅因子要求.
主要成果:
- 确定了类似O-甲基转移酶的蛋白质AlpH,它是负责氨酸在氨酸生物合成中的纳入的关键酶.
- AlpH催化了一种新型的,SAM-独立的L-glutamylhydrazine和一个多基基介质之间的合反应.
- 这种合通过在多基基生物合成的背景下,通过罕见的曼尼赫反应进行.
结论:
- 发现AlpH扩大了已知的O-甲基转移酶类酶的催化谱.
- 这项工作澄清了像金氨酸这样的天然产品的生物合成中的关键步骤.
- 这些发现为未来的基因组挖掘和合成生物学方法提供了基础,以发现和设计新的天然产品.
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