Novel biocatalytic reductions for synthesis of chiral amines

用于合成手性胺的新型生物催化还原

• 批准号: BB/D002826/1
• 负责人: Gillian Stephens
• 金额: $ 55.93万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FD002826%2F1
• 关键词: Novel; biocatalytic; reductions; synthesis; chiral

Chiral amines are used very widely as chemical intermediates to produce drug molecules. Chiral amines exist in more than one form, called enantiomers, and often only one of them is suitable for use in medicine. However, it is extremely difficult to produce the required enantiomer of many chiral amines by standard chemical techniques. It is much better to use enzymes to produce amines, because many enzymes produce pure enantiomers. However, there are still very few enzymes that are suitable for chiral amine production. In this project, we plan to develop new enzymes to produce chiral amines for drug manufacture. The enzymes are from bacteria that grow without oxygen(anaerobes). These bacteria have very unusual enzymes. The amine-producing enzymes that we have discovered catalyse a wide range of reactions that do not occur in other cells. The project will include purifying and characterising the enzymes. We shall also develop genetically engineered bacteria to use for amine manufacturing, because the anaerobes are not really suitable for use in industry. Ultimately, the new enzymes will make it possible to manufacture existing drugs much more cheaply. Furthermore, it should also become possible to produce new medicines that cannot be made at present.

手性胺作为生产药物分子的化学中间体被非常广泛地使用。手性胺以一种以上的形式存在，称为对映体，并且通常只有其中一种适合用于医学。然而，通过标准化学技术制备许多手性胺的所需对映体是极其困难的。用酶生产胺要好得多，因为许多酶产生纯的对映体。然而，仍然有非常少的酶适用于手性胺生产。本项目拟开发新的酶来生产手性胺用于药物生产。这些酶来自于无氧生长的细菌（厌氧菌）。这些细菌具有非常不寻常的酶。我们发现的胺生成酶催化了许多在其他细胞中不发生的反应。该项目将包括纯化和表征酶。我们还将开发基因工程细菌用于胺制造，因为厌氧菌并不真正适合在工业中使用。最终，新的酶将使更便宜地制造现有药物成为可能。此外，还应该能够生产目前无法生产的新药。

项目成果

Recombinant expression and characterisation of the oxygen-sensitive 2-enoate reductase from Clostridium sporogenes.

• DOI: 10.1099/mic.0.000568
• 发表时间: 2018-03
• 期刊: Microbiology (Reading, England)
• 作者: Mordaka PM;Hall SJ;Minton N;Stephens G
• 通讯作者: Stephens G

Asymmetric Reduction of Activated Alkenes by Pentaerythritol Tetranitrate Reductase: Specificity and Control of Stereochemical Outcome by Reaction Optimisation

• DOI: 10.1002/adsc.200900574
• 发表时间: 2009-11-01
• 期刊: ADVANCED SYNTHESIS & CATALYSIS
• 影响因子: 5.4
• 作者: Fryszkowska, Anna;Toogood, Helen;Scrutton, Nigel S.
• 通讯作者: Scrutton, Nigel S.