对CYP71AV1的功能分析揭示了素生物合成的进化格局
Fang-Yan Chen1,2, Qiu-Yan Mu3, Bing-Yi Xu3,4
1Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, Shandong, China.
Frontiers in plant science
|April 5, 2024
概括
错误识别了一种关键的酶在阿尔特米西宁生物合成. 这项研究揭示了一种阿莫法-4,11-二烯氧化酶 (AMO) 的副本实际上是一种生殖甲氧化酶 (GAO),澄清了Artemisia annua.中这种途径的演变.
科学领域:
- 植物生物化学和分子生物学
- 进化生物学是进化的生物学.
- 代谢途径工程是指代谢途径的工程.
背景情况:
- 在 *Artemisia annua* 中的阿尔特米西宁生物合成被认为是从祖先的costunolide路径进化而来的.
- 这种途径的进化历史,特别是特定酶的作用,仍然不完全理解.
- CYP71AV1 (amorpha-4,11-diene氧化酶,AMO) 是艺术素生物合成中的第一个氧化酶,并被认为是从生殖A氧化酶 (GAO) 专业化.
研究的目的:
- 为了研究 *Artemisia annua* *Artemisia annua* *Artemisinin和costunolide生物合成途径之间的进化关系.
- 为了澄清 *A. annua* 基因组中两个已识别的 AMO 副本的酶功能.
- 了解酶专业化和基因重复在新型代谢途径出现中的作用.
主要方法:
- 对 *Artemisia annua* AMO 副本与其他 GAO 的比较序列分析.
- 对AMO基因的组织特异性表达分析.
- 使用重组蛋白质进行体外酶分析以确定基质特异性和催化活性.
主要成果:
- 一个AMO的副本,被指定为AMOHAP,表现出不同的转录模式和与祖先GAO的序列相似性.
- 再组合的AMOHAP蛋白显示出明显的生殖基因甲氧化酶 (GAO) 活性,而不是无形-4,11-二烯氧化酶 (AMO) 活性.
- 由于AMOHAP在甲基-4,11-二烯上的无序活性,可能导致它在以前的研究中被错误分类.
- 相对于上游酶,AMOHAP的不同表达可能解释了costunolide生物合成的丧失.
结论:
- AMOHAP被确定为一种功能性GAO,而不是AMO,这挑战了关于素素路径演变的先前假设.
- 对AMOHAP的错误识别凸显了酶进化和专业化的复杂性.
- 这项研究提供了关于新代谢途径的出现如何可能涉及祖先酶的修改和重新使用的见解,导致更换旧的途径.
相关概念视频
01:19Allosteric Proteins-ATCase
5.7K
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
5.7K
01:28Structure-Activity Relationships and Drug Design
716
Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
716