在自然产品的生物合成中酶催化 [6+4] 循环添加物
Bo Zhang1, Kai Biao Wang1, Wen Wang1
1State Key Laboratory of Pharmaceutical Biotechnology, Institute of Functional Biomolecules, School of Life Sciences, Nanjing University, Nanjing, China.
Nature
|March 15, 2019
概括
酶催化环周性 [6+4] 循环添加,这是天然产品生物合成的关键步骤. 这一发现揭示了如何通过单一的双模转变状态促进复杂反应.
科学领域:
- 有机化学
- 生物化学
- 酵素学
背景情况:
- 经循环反应对于合成和生物合成中的化学键的形成至关重要.
- 迪尔斯-阿尔德 ([4+2]) 循环加法是常见的,但像 [6+4] 这样的高阶循环加法仍然具有挑战性.
- 建议使用酶催化 [6+4] 循环添加剂,但未经实验证实.
研究的目的:
- 为了证明酶催化循环 [6+4] 循环添加在链杆菌素生物合成.
- 阐明对双模转变状态起作用的环环酶的机制.
- 研究循环添加产品的酶转化为天然产品.
主要方法:
- 酶表征和结构分析 (晶体结构).
- 计算模拟 (潜在能量,分子动力学).
- 检测反应机制的位点定向突变.
主要成果:
- 在天然产品生物合成中证明了 [6+4] 循环添加的酶催化.
- 显示的环环酶通过单个双模过渡状态催化了 [6+4] 和 [4+2] 循环添加.
- 阐明了Cope重组和酶转化到最终产品的机制.
结论:
- 酶可以催化复杂的环周期性 [6+4] 循环添加.
- 循环利用一个单一的双模转换状态来实现多个循环添加路径.
- 这项工作提供了对酶催化周期反应的机理洞察.
更多相关视频
09:08From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes Tü6028
Published on: January 13, 2017
17.8K
07:12Cercosporin-Photocatalyzed [4+1]- and [4+2]-Annulations of Azoalkenes Under Mild Conditions
Published on: July 17, 2020
6.7K
相关概念视频
Enzymes
94.6K
Inside living organisms, enzymes act as catalysts for many biochemical reactions involved in cellular metabolism. The role of enzymes is to reduce the activation energies of biochemical reactions by forming complexes with its substrates. The lowering of activation energies favor an increase in the rates of biochemical reactions.
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...
94.6K
[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction
12.2K
The Diels–Alder reaction is an example of a thermal pericyclic reaction between a conjugated diene and an alkene or alkyne, commonly referred to as a dienophile. The reaction involves a concerted movement of six π electrons, four from the diene and two from the dienophile, forming an unsaturated six-membered ring. As a result, these reactions are classified as [4+2] cycloadditions.
12.2K
Enzyme Kinetics
104.0K
Enzymes speed up reactions by lowering the activation energy of the reactants. The speed at which the enzyme turns reactants into products is called the rate of reaction. Several factors impact the rate of reaction, including the number of available reactants. Enzyme kinetics is the study of how an enzyme changes the rate of a reaction.
Scientists typically study enzyme kinetics with a fixed amount of enzyme in the controlled environment of a test tube. When more reactant, or substrate, is...
Scientists typically study enzyme kinetics with a fixed amount of enzyme in the controlled environment of a test tube. When more reactant, or substrate, is...
104.0K
Biosynthesis in Bacteria
652
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,...
652
Biosynthesis of Polysaccharides
611
Polysaccharides such as glycogen and starch are synthesized from nucleoside diphosphate sugars, primarily uridine diphosphate glucose (UDPG) and adenosine diphosphate glucose (ADPG). These activated glucose donors act as key intermediates in carbohydrate metabolism and biosynthesis. UDPG primarily involves glycogen synthesis in animals and many bacteria, while ADPG plays a fundamental role in starch synthesis in plants and certain bacteria.UDPG is formed when glucose-1-phosphate reacts with...
611
Biosynthesis of Lipids
568
Microbial membranes exhibit remarkable diversity in lipid composition, reflecting evolutionary adaptations to various environmental conditions. The three domains of life—Bacteria, Archaea, and Eukarya—synthesize membrane lipids through distinct biosynthetic pathways, leading to fundamental structural differences that impact membrane stability, function, and adaptability.Fatty Acid-Based Lipids in Bacteria and EukaryaBacteria and eukaryotes share a common fatty acid biosynthesis...
568
