区域特定的基酶和O-甲基转移酶用于Tabernaemontana elegans (青树) 中抗癌类的生物合成
Scott Galeung Alexander Mann1, Matthew Bailey Richardson1, Rochelle Nicola Young1
1Department of Chemistry, University of New Brunswick, Fredericton, NB, E3B 5A3, Canada.
Plant physiology and biochemistry : PPB
|June 24, 2025
概括
研究人员发现了两个酶,TeC11H和TeHCOMT,来自Tabernaemontana elegans.研究人员发现了两个酶,TeC11H和TeHCOMT,来自Tabernaemontana elegans.研究人员发现了两个酶,TeC11H和TeHCOMT,来自Tabernaemontana elegans.研究人员发现了两个酶,TeC11H和TeHCOMT. 这些酶可以通过特定的甲氧化产生强大的抗癌和抗自的 bis-monoterpenoid 醇类化合物 (bis-MIAs).
科学领域:
- 自然产品生物合成 自然产品生物合成
- 酶学 是一种酶学.
- 药用化学 医学化学
背景情况:
- 单类醇类化合物 (MIAs) 是具有重要的药用价值的多样化的天然产品.
- 比斯-MIAs,像文布拉斯一样,是由单体MIAs的酶合形成的,通常需要激活的反应中心.
- 塔伯纳蒙塔纳伊莱根斯 (Tabernaemontana elegans) 生产具有抗癌和抗自活动的bis-MIA.
研究的目的:
- 在Tabernaemontana elegans中识别和描述负责bis-MIA生物合成的酶.
- 阐明冠状腺素激活中的区域特异性甲氧化机制.
- 了解酶活性位点在不同区域选择性方面发生的进化适应.
主要方法:
- 酶识别和表征 (TeC11H 和 TeHCOMT).
- 对酶活性和基质特异性的生物化学分析.
- 同性学建模用于比较T. elegans和T. iboga酶的活性位点.
主要成果:
- 鉴定了来自T. elegans的冠状腺11-基酶 (TeC11H) 和11-基冠状腺O-甲基转移酶 (TeHCOMT).
- 证明了冠状腺素的C11-甲氧化激活了bis-MIA形成的内醇环.
- 在T. elegans和T. iboga酶中显示出明显的区域选择性,这是由于关键的活性部位残留物,有利于C11或C10甲氧化分别.
结论:
- 鉴定到的酶对 (TeC11H和TeHCOMT) 对于合成T. elegans.中的11-甲基冠利丁衍生 bis-MIAs至关重要.
- 酶活性位点的特异性决定了区域选择性甲氧化,突出了协调进化.
- 这些酶为新型抗癌和抗自性bis-MIAs的代谢工程提供了潜力.
相关概念视频
01:17Phase II Reactions: Methylation Reactions
370
Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
370
01:15Drugs that Stabilize Microtubules
2.1K
Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.1K
01:28Biosynthesis of Nucleic Acids
204
Nucleic acid biosynthesis is a fundamental biochemical process that produces the purine and pyrimidine nucleotides essential for DNA and RNA synthesis. This pathway maintains a balanced nucleotide pool, preventing imbalances that could jeopardize genetic integrity and cellular function. Given the crucial role of nucleotides, their synthesis is tightly regulated to ensure proper cellular homeostasis.Purine BiosynthesisThe biosynthesis of purine nucleotides begins with ribose-5-phosphate, a...
204
01:37Epigenetic Regulation
3.1K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.1K
01:19Allosteric Proteins-ATCase
5.9K
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...
5.9K
01:10Drugs that Destabilize Microtubules
2.0K
Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
2.0K