Elucidating and Engineering Legonmycin Biosynthesis: a framework for heterobicyclic biotransformation

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Many currently used drugs that we rely on for the treatment of cancer, bacterial infection, immune disorders and viral infections are either natural products or are derived from natural products. As such natural products still remain the major source of lead compounds for the development of new drugs and diagnostic molecules. However, natural products are often complex in terms of structure and composition making them difficult for synthetic chemists to access and thus develop further. In contrast bacteria can possess an amazing inventory of complex chemistry that organic chemists only dream of. In making new molecules, a key challenge is often to identify plausible new scaffolds or motifs (also known as chemical diversity) which is at the heart of drug discovery. We are going to study two bacterial enzymes that have the capability to convert linear peptide into heterobicyclic molecules under mild reactive conditions. These heterobicyclic ring systems are a common motif in biologically important compounds but there does not have any good way of making them by synthetic chemistry. The use of the bacterial enzymes to accomplish chemical tasks is well established in food industry and the benefits in terms of sustainable manufacturing are well document. However, the application of enzymatic process/ industrial biotechnology processes are still under developed the fine chemical, pharmaceutical and agricultural industries. By working out the catalytic capabilities of the two enzymes we will gain the ability to develop their industrial biotechnological potential. In doing this, we will be able to make novel building blocks (also known as scaffolds) and, access new biologically active compounds.