多酶级联用于有效地将dl-Pantolactone脱血化为d-Pantolactone
Lijun Jin1, Xun Liu1, Tairan Wang1
1Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China.
Molecules (Basel, Switzerland)
|July 29, 2023
概括
一个新的三种酶级联有效地将dl-pantolactone脱血为d-pantolactone,这是一个关键的维生素B5前体. 这种更绿色的方法使用全细胞生物催化剂实现了高光学纯度.
科学领域:
- 生物催化和酶工程 生物催化和酶工程
- 化学合成 化学合成
- 可持续化学 可持续化学
背景情况:
- D-pantolactone是合成d-pantothenic acid (维生素B5) 的重要中间体.
- 目前的商业合成依赖于动态分辨率,效率较低.
- 脱化提供了一种更简单,更绿色,更可持续的途径,以获得高纯度的d-pantolactone.
研究的目的:
- 开发一种高效的三种酶级联,用于dl-pantolactone的脱血.
- 为了提高可持续性和简单性,利用全细胞生物催化剂.
- 为了实现d-pantolactone的高光学纯度和生产率.
主要方法:
- 三种酶的同时表达:E. coli中的l-pantolactone脱酶 (AmeLPLDH),合聚缩酶 (ZpaCPR) 和葡萄糖脱酶 (BsGDH).
- 开发一种用于序列催化的三种酶级联:从l-pantolactone变成ketopantolactone,然后从ketopantolactone变成d-pantolactone.
- 使用葡萄糖脱水酶和葡萄糖在全细胞生物催化剂中的局部辅酶再生.
主要成果:
- 成功开发了一种高效的三种酶级联,用于dl-pantolactone脱血.
- 整个细胞生物催化剂实现了对d-pantolactone的98.6%的高反体过剩 (e.e.p).
- 在优化条件下,经过36小时的脱血后,生产率为107.7g/l·d.
结论:
- 开发的三种酶级联代表了d-pantolactone的可持续生产的重大进展.
- 使用共同表达酶的全细胞生物催化剂为工业应用提供了实用和高效的方法.
- 这种方法为传统合成提供了更绿色的替代方案,产生高纯度的d-pantolactone.
相关概念视频
Preparation of Diols and Pinacol Rearrangement
3.4K
Compounds bearing two hydroxyl groups are known as diols. When the hydroxyl groups are located on adjacent carbon atoms, the diols are called vicinal diols or glycols. Under acidic conditions, vicinal diols undergo a specific reaction called pinacol rearrangement.
The reaction begins with transferring a proton from the acid catalyst to one of the hydroxyl groups, producing an oxonium ion.
The reaction begins with transferring a proton from the acid catalyst to one of the hydroxyl groups, producing an oxonium ion.
3.4K
Alkylation of β-Diester Enolates: Malonic Ester Synthesis
3.4K
Malonic ester synthesis is a method to obtain α substituted carboxylic acids from ꞵ-diesters such as diethyl malonate and alkyl halides.
3.4K
Loss of Carboxy Group as CO2: Decarboxylation of Malonic Acid Derivatives
2.0K
Just like β-keto acids—which upon thermal decarboxylation form ketones—β-dicarboxylic acids undergo decarboxylation to generate monocarboxylic acids with the liberation of carbon dioxide.
2.0K
Crossed Aldol Reaction Using Strong Bases: Directed Aldol Reaction
2.2K
The reaction between two different carbonyl compounds comprising α hydrogen in the presence of a strong base like lithium diisopropylamide (LDA) to form a crossed aldol product is known as a directed aldol reaction. The directed aldol reaction is depicted in Figure 1.
2.2K
Intramolecular Claisen Condensation of Dicarboxylic Esters: Dieckmann Cyclization
2.5K
Dieckmann cyclization is an intramolecular Claisen condensation of diesters. The reaction occurs in the presence of a base and generates a cyclic β-ketoester as the final product. Commonly, 1, 6 and 1, 7-diesters are preferred substrates for the reaction since the generated five, and six-membered cyclic β-keto esters are particularly more stable.
2.5K
Phase I Reactions: Hydrolytic Reactions
163
Hydrolysis, a cornerstone of phase I biotransformation reactions, uses water to cleave chemical bonds. This process is pivotal in drug metabolism, generating more polar metabolites that can be easily excreted.
An important hydrolytic reaction is ester hydrolysis. Ester bonds, often found in prodrugs, are broken down, increasing the solubility of drugs like aspirin and lidocaine for more straightforward elimination. Amide hydrolysis is another critical reaction, targeting amide bonds prevalent...
An important hydrolytic reaction is ester hydrolysis. Ester bonds, often found in prodrugs, are broken down, increasing the solubility of drugs like aspirin and lidocaine for more straightforward elimination. Amide hydrolysis is another critical reaction, targeting amide bonds prevalent...
163


