Exploring the mechanism and scope of the enzymatic formation of five membered ring

今天我们用于治疗癌症、细菌感染、免疫紊乱和病毒感染的许多药物要么是天然产物，要么是从天然产物中提取的。即使在今天，天然产物仍然是药物和诊断分子的来源。与人造化学品相比，天然产品在形状和组成方面都很复杂。这种结构上的新颖性是它们以特定方式起作用的部分原因（副作用较小）。一般来说，这些天然产物是由细菌而不是人类或动物制造的。人类已经进化到放弃了很多复杂的化学反应。我们需要食物中的维生素，因为我们无法制造它们；而是依靠细菌或植物来制造它们，我们吃它们。细菌具有令人惊叹的复杂化学反应，这是有机化学家梦寐以求的。在制造新的人造材料时，一个关键的挑战往往是确定合理的新支架或骨架。容易画出来的分子很难做出来。然而，新的支架和基序（称为化学多样性）是药物发现的核心。我们将研究制造杂环氨基酸的细菌酶。这些五元环是生物活性化合物中常见的基序，但目前还没有很好的方法在天然产物中通过合成化学来制造它们。利用细菌酶来完成化学任务是众所周知的，洗衣粉是最著名的例子，但它们在食品工业和越来越多的有机化学实验室中广泛使用。通过弄清制造五元环的酶是如何工作的，我们将获得对这种酶的控制。通过这样做，我们将能够制造出新的材料，我们相信是全新的生物活性化合物。更重要的是，这些酶在室温下在水中工作，不会产生有害的废物。

Many of todays drugs that we rely on for treatment of cancer, bacterial infection, immune disorders and viral infections are either natural products or are derived from natural products. Natural products remain, even today, a source of drugs and diagnostic molecules. In contrast to man made chemicals natural products are complex in terms of shape and composition. This structural novelty is in part the reason that they work in specific ways, (less side effects). In general, these natural products are made in bacteria rather than in humans or animals. Humans have evolved to ditch much of their complex chemistry. We need vitamins in food, because we cannot make them; rather rely on bacteria or plants to make them and we eat them. Bacteria have an amazing repetoire of complex chemistry that organic chemists can only dream of. In making new man made materials, a key challenge is often to identify plausible new scaffolds or skeletons. Molecules which are easy to draw are hard to make. Yet new scaffolds and motifs (known as chemical diversity) is at the heart of drug discovery. We are going to study the bacterial enzyme that makes heterocyclic amino acids. These five membered rings are a common motif in biologically active compounds but there does not exist any good way of making them in natural products by synthetic chemistry. The use of bacterial enzymes to accomplish chemical tasks is very well known, washing powder being the best known example but they are widespread in the food industry and increasingly the organic chemistry lab. By working out how the enzyme which makes five membered rings works, we will gain control of the enzyme. By doing this we will be able to make novel materials and we believe completely new biologically active compounds. What is more these enzymes work in water at room temperature without producing noxious waste materials.