Creating a user friendly Transaminase toolkit

创建用户友好的转氨酶工具包

• 批准号: EP/G005834/1
• 负责人: John Ward
• 金额: $ 16.21万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FG005834%2F1
• 关键词: Creating; user; friendly; Transaminase; toolkit

Many drugs to treat the wide range of diseases and conditions are complex molecules, which contain what are termed biologically active groups. One of the most important biologically active groups in many drug molecules is the amine group. Indeed, 70% of all pharmaceuticals contain derivatives of chiral amines and the global market of chiral amines is estimated as 4 bn/annum. It is often non-trivial and expensive for organic chemists to make complex drug molecules and put the amine group in the correct position or in the correct relationship to other parts of the molecule. Some chemical procedures to introduce the amine group can be harsh and disrupt or modify the other part of the drug molecule. However, enzymes can be used to introduce the amine group into selective positions in drug molecules. Enzymes are proteins and are biological catalysts, often termed biocatalysts. They are usually very specific as to where they will place the amine group and they carry out their reaction under mild conditions. They are also a renewable resource and are biodegradable unlike some chemical reagents. These enzymes that can put an amine group into a drug molecule are called transaminases.In this project we will find new transaminase enzymes that are able to introduce the amine moiety into complex drug molecules. Then we will put the genes for these new transaminases in to a laboratory bacterium that can be grown in large amounts to create a renewable source of the transaminases. We will investigate how to put transaminases with different specificities towards different molecules, into kits that chemists who carry out research into creating new drugs, can use. These kits will allow chemists to try out different transaminases on the compound they might be working on and if they find one that works at the small scale used in the laboratory, they can use that transaminse in a larger scale process.We want to encourage the use of transaminase biocatalysts in the synthesis of drugs and other chemicals as this will be a more atom efficient process for making complex drugs and chemicals of the future, with less environmental impact.

许多治疗各种疾病和病症的药物是复杂的分子，其含有所谓的生物活性基团。许多药物分子中最重要的生物活性基团之一是胺基。实际上，70%的药物含有手性胺的衍生物，并且手性胺的全球市场估计为40亿/年。对于有机化学家来说，制造复杂的药物分子并将胺基放在正确的位置或与分子的其他部分保持正确的关系通常是不平凡和昂贵的。一些引入胺基的化学过程可能是苛刻的，并且会破坏或改变药物分子的其他部分。然而，酶可用于将胺基引入药物分子中的选择性位置。酶是蛋白质，是生物催化剂，通常称为生物催化剂。它们通常对胺基的位置非常具体，并且在温和的条件下进行反应。它们也是一种可再生资源，与某些化学试剂不同，它们是可生物降解的。这些能够将氨基引入药物分子的酶被称为转氨酶。在这个项目中，我们将找到能够将氨基引入复杂药物分子的新转氨酶。然后，我们将把这些新的转氨酶的基因放入一种实验室细菌中，这种细菌可以大量生长，以创造转氨酶的可再生来源。我们将研究如何将对不同分子具有不同特异性的转氨酶放入试剂盒中，供化学家研究创造新药时使用。这些试剂盒将允许化学家在他们可能正在研究的化合物上尝试不同的转氨酶，如果他们发现一种在实验室中小规模使用的转氨酶，他们可以在更大规模的过程中使用转氨酶。我们希望鼓励在药物和其他化学品的合成中使用转氨酶生物催化剂，因为这将是一个更原子效率的过程，用于制造复杂的药物和化学品。未来，对环境的影响更小。

项目成果

Non-linear kinetic modelling of reversible bioconversions: Application to the transaminase catalyzed synthesis of chiral amino-alcohols

• DOI: 10.1016/j.bej.2013.01.010
• 发表时间: 2013-04
• 期刊: Biochemical Engineering Journal
• 影响因子: 3.9
• 作者: L. Rios‐Solis;N. Bayir;M. Halim;C. Du;J. Ward;F. Baganz;G. Lye

The substrate specificity, enantioselectivity and structure of the (R)-selective amine : pyruvate transaminase from Nectria haematococca.

• DOI: 10.1111/febs.12778
• 发表时间: 2014-05
• 期刊: The FEBS journal
• 作者: Sayer C;Martinez-Torres RJ;Richter N;Isupov MN;Hailes HC;Littlechild JA;Ward JM
• 通讯作者: Ward JM

TTC-based screening assay for ?-transaminases: a rapid method to detect reduction of 2-hydroxy ketones.

基于 TTC 的 β-转氨酶筛选测定：检测 2-羟基酮还原的快速方法。

• DOI: 10.1016/j.jbiotec.2011.12.023
• 发表时间: 2012
• 期刊: Journal of biotechnology
• 影响因子: 4.1
• 作者: Sehl T

Enzymatic synthesis of chiral amino-alcohols by coupling transketolase and transaminase-catalyzed reactions in a cascading continuous-flow microreactor system.

• DOI: 10.1002/bit.26470
• 发表时间: 2018-03
• 期刊: Biotechnology and bioengineering
• 影响因子: 3.8
• 作者: Gruber P;Carvalho F;Marques MPC;O'Sullivan B;Subrizi F;Dobrijevic D;Ward J;Hailes HC;Fernandes P;Wohlgemuth R;Baganz F;Szita N
• 通讯作者: Szita N

Data on a thermostable enzymatic one-pot reaction for the production of a high-value compound from l-arabinose.

• DOI: 10.1016/j.dib.2018.05.140
• 发表时间: 2018-08
• 期刊: Data in brief
• 影响因子: 1.2
• 作者: Bawn M;Subrizi F;Lye GJ;Sheppard TD;Hailes HC;Ward JM
• 通讯作者: Ward JM