チューブリン結合アルカリドコルキシンの総生物合成
Ryan S Nett1,2, Elizabeth S Sattely1,2
1Department of Chemical Engineering, Stanford University, Stanford, California 94305, United States.
Journal of the American Chemical Society
|November 15, 2021
まとめ
研究者はコルキシン生物合成の完全な代謝経路を解明し,Gloriosa superbaの重要な酵素を発見しました. この突破は モデル植物における この重要な抗炎症薬の 完全な生物合成を可能にします
科学分野:
- 生物化学
- 植物科学
- 薬理学について
背景:
- コルヒシンは,痛風性関節炎のような炎症を治療するために使用される植物性アルカロイドです.
- 治療効果は微小管の形成を阻害し,抗炎症とミトーシス毒の両方として作用します.
- コルキシン生物合成の理解は,生化学における長年の課題である.
研究 の 目的:
- コルキシン生物合成に 責任のある酵素機構の発見と特徴付け
- コルキシン生成のための完全な代謝経路を再構成する.
- コルヒシンの異質生産と代謝工学を可能にします.
主な方法:
- グロリオサ・スーパーバの酵素発見
- メタボリック経路の再構成 in vitro
- モデルプラントでの異種生産による全生物合成
主要な成果:
- トロポロン中間物質を改変する3つを含む複数の経路酵素の特定
- コルキシンへの完全な代謝経路の成功再構成 (1).
- 主な代謝産物からのエナンチオプア (-) - コルキシンの全生物合成の実証
結論:
- コルキシン生物合成の酵素的基礎は,現在広く理解されている.
- ヘテロログな生産は,この薬用アルカロイドの代謝工学の道を開く.
- 遅い段階の改変に関する洞察は,原生植物におけるアルカロイドの生物学的役割とのつながりを示唆しています.
さらに関連する動画
関連する概念動画
Drugs that Destabilize Microtubules
2.1K
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...
2.1K
Drugs that Stabilize Microtubules
2.2K
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...
2.2K
Biosynthesis of Nucleic Acids
307
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...
307
Microtubule Formation
6.3K
Microtubules are dynamic structures that undergo continuous assembly and disassembly. They originate from specialized multi-protein complexes known as microtubule organizing centers or MTOCs. Within the MTOC, the point of origin of the microtubule is known as the minus end, while the end radiating outward is the plus end. Microtubules serve two primary functions — the organization of spindle complexes to separate sister chromatids during mitotic or meiotic cell division and the formation...
6.3K
Biosynthesis in Bacteria
188
Biosynthesis in bacteria is a fundamental anabolic process that generates essential macromolecules, including proteins, nucleic acids, lipids, and polysaccharides. These macromolecules are critical for cellular growth, replication, and function. The process is tightly regulated and energetically linked to catabolic pathways to ensure optimal resource utilization.Biosynthetic pathways begin with precursor metabolites such as pyruvate, acetyl-CoA, and glucose-6-phosphate derived from glycolysis,...
188
Allosteric Proteins-ATCase
6.0K
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...
6.0K


