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

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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.