在Aconitum中,不同的多功能P450s赋能生物活性的tripterifordin和神秘的atiserenoids的生物合成意味着融合的进化
Fei Luo1, Qian Zhou1, Feilong Chen1
1Shenzhen Key Laboratory of Plant Genetic Engineering and Molecular Design, SUSTech-PKU Institute of Plant and Food Science, Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong, China.
Nature communications
|July 2, 2025
概括
研究人员确定了关键酶,合成酶 (TPSs) 和细胞染色体P450s,这些酶在阿科尼植物中产生多种生物活性二甲. 这一发现为合成诸如二等有价值的化合物提供了新的途径.
科学领域:
- 生物化学 生物化学
- 自然产品生物合成 自然产品生物合成
- 植物分子生物学 植物分子生物学
背景情况:
- 迪特尔类物质具有显著的结构多样性和生物活性,主要受到合成酶 (TPSs) 和单氧化酶的细胞染色体P450的影响.
- 甲烯和乙烯支架对于合成生物活性二甲和类化合物至关重要,这些生物活性二甲和类化合物存在于Aconitum物种中,如3 - 乙氨基和关基A.
- 在这些二烯基支架的结构和功能多样化中,P450酶的特定作用仍然在很大程度上未被描述.
研究的目的:
- 识别和功能性表征合成酶 (TPSs) 和参与Aconitum物种中二类生物合成的P450单氧化酶.
- 阐明P450多样化二烯结构和功能的机制.
- 探索特定的四类和新型衍生物的组合生物合成的潜力.
主要方法:
- 挖掘Aconitum carmichaelii和Aconitum coreanum的转录组,以确定候选TPS和P450基因.
- 通过体外和体外测定确定TPS和P450酶的功能验证.
- 蛋白质分析和位点定向突变发生,以了解P450酶活性和基质特异性.
- 组合生物合成以产生目标二甲和新型类似物.
主要成果:
- 确定了9个TPS,它们能够产生甲,乙,或16α-氧-甲支架.
- 发现了14种P450酶,其中8种表现出多功能活性,在7个不同的部位催化氧化.
- 确定了影响P450活性和产品概况的关键氨基酸残留物.
- 组合生物合成产生了tripterifordin,guan-fu diterpenoid A和14种新型的atiserenoids,其中一些具有等位基效应.
- 观察到三的融合生物合成,该化合物在A. coreanum中检测到,类似于其在Tripterygium wilfordii中的存在.
结论:
- 细胞染色体P450酶在催化选择性二烯氧化过程中表现出显著的可塑性.
- 已识别的TPS和P450酶为访问tripterifordin及其衍生物提供了基础.
- 这些发现为合成生物学方法开辟了道路,以阐明下游的二二生物合成途径.
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