在拉萨洛酸A的生物合成中形成聚乙烯的环氧化酶Lsd19:在聚乙烯生物合成中对聚-聚氧化假设的直接实验证据
Yoshihiro Shichijo1, Akira Migita, Hiroki Oguri
1Division of Chemistry, Graduate School of Science, Hokkaido University, Sapporo 060-0810, Japan.
Journal of the American Chemical Society
|August 20, 2008
概括
研究人员确定了Lsd19酶,该酶对于形成像lasalocid.lasalocid这样的聚乙烯天然产品至关重要. 这项研究提供了在聚生物合成中酶性环氧化物开放的第一个实验证据,揭示了6-endo-tet循环化机制.
科学领域:
- 生物化学 生物化学
- 自然产品生物合成 自然产品生物合成
- 酶学 是一种酶学.
背景情况:
- 聚乙烯代谢物是具有复杂结构的重要自然产品.
- 了解聚乙烯骨架结构背后的酶机制仍然是有机化学中的一个重大挑战.
- 缺乏关于酶性聚乙烯形成的实验数据.
研究的目的:
- 阐明聚乙烯天然产品生物合成的酶途径.
- 为了识别和描述负责激素的关键循环化步骤在拉萨洛形成.
- 为在聚乙烯生物合成中提供酶性环氧化物开放的第一个实验证据.
主要方法:
- 克隆和过度表达的假定环氧化酸酶基因lsd19从大肠杆菌的酸盐生物合成基因集群.
- 净化Lsd19酶. 这是一个很好的方法.
- 酶转化试验使用拟议的基质 - - 双基和其合成的模拟物.
- 用三酸对双氧化物的化学处理进行比较.
主要成果:
- 净化后的Lsd19酶成功地通过6-endo-tet循环转化模式将双双氧普拉萨洛酸转化为拉萨洛酸A.
- 一种合成的模拟物也被Lsd19转化为其衍生物,证实了其催化活性.
- 通过化学处理,通过5-exo-tet循环,产生了isolasalocid A,突出了该酶的特定机制.
- 这项研究提供了一个明确的证据,证明 bisepoxyprelasalocid 是一种生物合成中间体.
结论:
- 酶Lsd19在拉萨酸生物合成中催化了连续的循环乙烯形成.
- Lsd19促进了能量不利的6-endo-tet循环,这是聚乙烯形成的新发现.
- 这项工作代表了第一个酶的环氧化物开放反应的演示,导致了聚乙烯天然产品.
- 这些发现为复杂的聚乙烯天然产品的生物合成提供了关键的见解.
相关概念视频
03:00Preparation of Epoxides
Overview
Epoxides result from alkene oxidation, which can be achieved by a) air, b) peroxy acids, c) hypochlorous acids, and d) halohydrin cyclization.
Epoxidation with Peroxy Acids
Epoxidation of alkenes via oxidation with peroxy acids involves the conversion of a carbon–carbon double bond to an epoxide using the oxidizing agent meta-chloroperoxybenzoic acid, commonly known as MCPBA. Since the O–O bond of peroxy acids is very weak, the addition of electrophilic oxygen of peroxy acids to...
Epoxides result from alkene oxidation, which can be achieved by a) air, b) peroxy acids, c) hypochlorous acids, and d) halohydrin cyclization.
Epoxidation with Peroxy Acids
Epoxidation of alkenes via oxidation with peroxy acids involves the conversion of a carbon–carbon double bond to an epoxide using the oxidizing agent meta-chloroperoxybenzoic acid, commonly known as MCPBA. Since the O–O bond of peroxy acids is very weak, the addition of electrophilic oxygen of peroxy acids to...
02:24Acid-Catalyzed Ring-Opening of Epoxides
Epoxides that are three-membered ring systems are more reactive than other cyclic and acyclic ethers. The high reactivity of epoxides originates from the strain present in the ring. This ring strain acts as a driving force for epoxides to undergo ring-opening reactions either with halogen acids or weak nucleophiles in the presence of mild acid. The acid catalyst converts the epoxide oxygen, a poor leaving group, into an oxonium ion, a better leaving group, making the reaction feasible. The...
02:04Oxidation of Alkenes: Anti Dihydroxylation with Peroxy Acids
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02:26Base-Catalyzed Ring-Opening of Epoxides
Due to their highly strained structures, epoxides can readily undergo ring-opening reactions through nucleophilic substitution, either in the presence of an acid or a base. The nucleophilic substitution reactions in the presence of acid are called acid-catalyzed ring-opening reactions, and nucleophilic substitution reactions in the presence of a base are called base-catalyzed ring-opening reactions. Epoxides undergo base-catalyzed ring-opening reactions in the presence of a strong nucleophile...
02:57Sharpless Epoxidation
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02:38Structure and Nomenclature of Epoxides
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