Creating a user friendly Transaminase toolkit

许多治疗各种疾病和病症的药物都是复杂分子，其中包含所谓的生物活性基团。在许多药物分子中，最重要的生物活性基团之一是胺基。事实上，70%的药品含有手性胺的衍生物，全球手性胺的市场估计为40亿美元/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其他部分建立正确的关系，往往是一件非常困难和昂贵的事情。一些引入胺基的化学过程可能是苛刻的，并且会破坏或修饰药物分子的其他部分。然而，酶可以将胺基引入药物分子的选择性位置。酶是蛋白质，是生物催化剂，通常称为生物催化剂。它们通常对放置胺基的位置非常明确，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。这些能将胺基放入药物分子中的酶被称为转氨酶。在这个项目中，我们将找到新的转氨酶，能够将胺部分引入复杂的药物分子。然后，我们将这些新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。我们将研究如何将具有不同特异性的转氨酶用于不同的分子，并将其放入进行新药研究的化学家可以使用的试剂盒中。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，如果他们在实验室中找到一种在小规模使用中有效的转氨酶，他们就可以在更大规模的过程中使用该转氨酶。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，因为这将是制造未来复杂药物和化学品的更有效的原子过程，对环境的影响更小。

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.