在Platensimycin生物合成中启动P450催化氧化
Jeffrey D Rudolf1, Liao-Bin Dong1, Xiao Zhang1
1Department of Chemistry , The Scripps Research Institute , Jupiter , Florida 33458 , United States.
Journal of the American Chemical Society
|September 15, 2018
概括
普拉坦西米辛 (PTM) 使用独特的以太结合来提高功效. 这项研究揭示了PtmO5酶
科学领域:
- 自然产品生物合成
- 酵素学
- 有机化学
背景情况:
- 平坦西 (PTM) 和平坦 (PTN) 是抑制脂肪酸合成的天然产品.
- PTM的功效和选择性与PTN中没有发现的独特乙醇部分有关.
- 之前的研究发现PtmT3是二烯合成酶,并将PtmO5与形成有关.
研究的目的:
- 阐明胺生物合成中以太部分形成的酶机制.
- 描述细胞P450酶PtmO5在这个过程中的作用.
主要方法:
- 在PtmO5酶的体外表征.
- 对PtmO5的基质特异性和反应产物的分析.
- 确定化和以太形成的立体化学.
主要成果:
- PtmO5 立体选择性地化了甲支架的 C-11 位置.
- 这种化生成一个11S,16R-二醇中间体.
- 在PTM中以太部分是通过这种二醇中间体的循环形成的,与C-11化过程中的氧.
结论:
- PtmO5 是一种关键的酶,催化了PTM的乙烯基部分所必需的立体选择性C-11化.
- 这项研究为天然产品生物合成中的新乙烯形成途径提供了详细的机制洞察力.
- 了解这种途径可以为新型脂肪酸合成酶抑制剂的设计提供信息.
相关概念视频
Ethers from Alcohols: Alcohol Dehydration and Williamson Ether Synthesis
12.9K
Overview
Ethers can be prepared from organic compounds by various methods. Some of them are discussed below,
Preparation of Ethers by Alcohol Dehydration
In this method, in the presence of protic acids, alcohol dehydrates to produce alkenes and ethers under different conditions. For example, in the presence of sulphuric acid, dehydration of ethanol at 413 K yields ethoxyethane, whereas it yields ethene at 443 K.
Ethers can be prepared from organic compounds by various methods. Some of them are discussed below,
Preparation of Ethers by Alcohol Dehydration
In this method, in the presence of protic acids, alcohol dehydrates to produce alkenes and ethers under different conditions. For example, in the presence of sulphuric acid, dehydration of ethanol at 413 K yields ethoxyethane, whereas it yields ethene at 443 K.
12.9K
Biosynthesis in Bacteria
675
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,...
675
Biosynthesis of Polysaccharides
641
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...
641
Biosynthesis of Lipids
594
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...
594
Initiation of Translation
39.0K
Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
39.0K
Initiation of Translation
8.1K
8.1K


