科尔奇因类生物合成的发现和工程
Ryan S Nett1,2, Warren Lau1, Elizabeth S Sattely3,4
1Department of Chemical Engineering, Stanford University, Stanford, CA, USA.
Nature
|July 24, 2020
概括
研究人员阐明了一种关键的抗炎药物素的植物生物合成途径. 他们在Gloriosa superba中发现了8个基因,
科学领域:
- 植物生物化学和药物化合物的生物合成.
- 代谢工程和合成生物学.
背景情况:
- 许多植物衍生疗法是直接从植物中分离出来的,其生物合成途径的知识并不完整.
- 美国食品和药物管理局批准的抗炎药物科尔奇辛来自特定的植物物种,但其生物合成尚未完全理解.
研究的目的:
- 在没有对基因,基因组或宿主遗传工具的先验知识的情况下,阐明了近乎完整的素生物合成途径.
- 鉴定参与形成胆固醇独特的环和药的关键基因和酶.
主要方法:
- 使用转录组学,代谢逻辑和途径重组来发现生物合成基因.
- 鉴定了来自Gloriosa superba的八个基因,负责合成N-formyldemecolcine,这是素的前体.
- 描述了一种新型的P450酶,催化了关键的环膨胀反应.
主要成果:
- 在Gloriosa superba中发现了N-formyldemecolcine生物合成的八个基因,这是素的前体.
- 鉴定了一种独特的非正规的P450细胞染色体,该细胞染色体参与了对素基架至关重要的环扩张.
- 在Nicotiana benthamiana中设计了一个16种酶路径,从氨酸和氨酸中产生N-formyldemecolcine.
结论:
- 确定了含有托罗波的类化合物的代谢途径.
- 从简单的氨基酸中产生复杂的生物活性化合物的植物代谢途径.
- 证明了在异种宿主中进行植物衍生药物生物合成的潜力.
相关概念视频
Drugs that Destabilize Microtubules
3.4K
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...
3.4K
Drug Discovery: Overview
10.7K
Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
10.7K
Chirality in Nature
16.2K
Chirality is the most intriguing yet essential facet of nature, governing life’s biochemical processes and precision. It can be observed from a snail shell pattern in a macroscopic world to an amino acid, the minutest building block of life. Most of the snails around the world have right-coiled shells because of the intrinsic chirality in their genes. All the amino acids present in the human body exist in an enantiomerically pure state, except for glycine - the sole achiral amino acid.
16.2K
Biosynthesis of Nucleic Acids
728
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...
728
Synthetic Biology
5.4K
Synthetic biology is an interdisciplinary science that involves using principles from disciplines such as engineering, molecular biology, cell biology, and systems biology. It involves remodeling existing organisms from nature or constructing completely new synthetic organisms for applications such as protein or enzyme production, bioremediation, value-added macromolecule production, and the addition of desirable traits to crops, to name a few.
Golden rice
Golden rice is a genetically modified...
Golden rice
Golden rice is a genetically modified...
5.4K
Drugs that Stabilize Microtubules
2.5K
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...
2.5K


