Harnessing the chemistry of natural product biosynthesis

Nature makes thousands of molecules – natural products – that have many applications in medicine and beyond. Plants in particular are an extremely important source of these molecules.Synthetic biology approaches are being used with increasing success to overproduce medicinally and agriculturally important plant-derived molecules inheterologous hosts.However, to pursue such approaches effectively, we must first fully understand the chemistry and biology of the biosynthetic pathways that generate these molecules. Given the complexity of plants and plant genomics, this pathway discovery process has been a major bottleneck in harnessing the chemical power of plants. Our researchaims to develop methods and resources to unlock the biosynthesis of complex molecules produced by plants. We are developing new omics methods to find these genes more efficiently. We also explore mechanisms by which these complex plant pathways have evolved to create extraordinary chemical diversity. Additionally, we also study examples in which Nature has made the same molecule twice. From these examples, we can compare and contrast two different chemical solutions that nature has evolved. We can then, in the laboratory, mix and match the two chemical pathways to design our own. Since important natural products from plants are often produced in very small quantities, or because the natural plant producers are hard to grow, it is important to develop metabolic engineering strategies to improve production of these compounds. This means that it is hard to get enough natural product to use in the clinic. Once we discover the genes that are responsible for making a natural product - for example, the anti-cancer drug vinblastine - we develop approaches to heterologously produce these products.