圆柱旋生物合成包括一个未激活的碳中心的功能化
Hitomi Nakamura1, Hilary A Hamer, Gopal Sirasani
1Department of Chemistry & Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, United States.
Journal of the American Chemical Society
|October 31, 2012
概括
研究人员确定了负责生产圆柱旋F的基因集群,这是一种具有独特碳支架的天然产品. 这一发现揭示了不同寻常的多基酸合成酶组合及其生物合成中涉及的宏循环形成.
科学领域:
- 自然产品生物合成 自然产品生物合成
- 化学生物学 化学生物学
- 基因组学就是基因组学.
背景情况:
- 圆柱旋是天然产品,其特点是具有独特的环旋碳脚手架.
- 了解复杂的自然产品的生物合成对于药物发现和合成生物学至关重要.
研究的目的:
- 为了确定生物合成基因集群,负责旋风F的生产.
- 阐明圆柱旋F组件背后的酶机制,包括多基酸合成酶活性和宏循环化.
主要方法:
- 基因组测序和生物信息分析以确定基因.
- 在体外酶表征以确定酶功能.
- 养研究以证实基因和产品形成之间的联系.
主要成果:
- 发现了一种特定的基因集群,参与了圆柱旋F生物合成.
- 阐明了一种不寻常的I型聚基酸合成酶组装线的启动和终止步骤.
- 宏观循环的形成被证明涉及一个未激活的碳中心的功能化.
结论:
- 鉴定出来的基因集群直接负责圆柱旋F的产生.
- 这项研究揭示了在天然产品生物合成中使用的新型酶策略,特别是在多基基组合和宏循环化中.
- 这项工作为合成或半合成生产圆筒cyclophanes提供了基础.
相关概念视频
Cycloaddition Reactions: Overview
Cycloadditions are one of the most valuable and effective synthesis routes to form cyclic compounds. These are concerted pericyclic reactions between two unsaturated compounds resulting in a cyclic product with two new σ bonds formed at the expense of π bonds. The [4 + 2] cycloaddition, known as the Diels–Alder reaction, is the most common. The other example is a [2 + 2] cycloaddition.
Cycloaddition Reactions: MO Requirements for Photochemical Activation
Some cycloaddition reactions are activated by heat, while others are initiated by light. For example, a [2 + 2] cycloaddition between two ethylene molecules occurs only in the presence of light. It is photochemically allowed but thermally forbidden.
Cycloaddition Reactions: MO Requirements for Thermal Activation
Thermal cycloadditions are reactions where the source of activation energy needed to initiate the reaction is provided in the form of heat. A typical example of a thermally-allowed cycloaddition is the Diels–Alder reaction, which is a [4 + 2] cycloaddition. In contrast, a [2 + 2] cycloaddition is thermally forbidden.
Pericyclic Reactions: Introduction
Pericyclic reactions are organic reactions that occur via a concerted mechanism without generating any intermediates. The reactions proceed through the movement of electrons in a closed loop to form a cyclic transition state, where rearrangement of the σ and π bonds yields specific products.
Pericyclic reactions can be classified into three categories: electrocyclic reactions, cycloaddition reactions, and sigmatropic rearrangements. Electrocyclic reactions and sigmatropic rearrangements are...
Pericyclic reactions can be classified into three categories: electrocyclic reactions, cycloaddition reactions, and sigmatropic rearrangements. Electrocyclic reactions and sigmatropic rearrangements are...
Photochemical Electrocyclic Reactions: Stereochemistry
The absorption of UV–visible light by conjugated systems causes the promotion of an electron from the ground state to the excited state. Consequently, photochemical electrocyclic reactions proceed via the excited-state HOMO rather than the ground-state HOMO. Since the ground- and excited-state HOMOs have different symmetries, the stereochemical outcome of electrocyclic reactions depends on the mode of activation; i.e., thermal or photochemical.
Selection Rules: Photochemical Activation
Selection Rules: Photochemical Activation
Aldehydes and Ketones with HCN: Cyanohydrin Formation Overview
Cyanohydrins are compounds that contain –CN and –OH groups on the same carbon atom. They are formed by the nucleophilic addition of the cyanide ions to the carbonyl group. Cyanide ions are highly basic and nucleophilic and can be generated from HCN under aqueous conditions. However, since HCN is a weak acid, the number of cyanide ions generated is very small. Hence, a small amount of base or KCN/NaCN is added to HCN to increase the concentration of the cyanide ions in the reaction mixture.


