Unlocking the chemical potential of plants: Predicting function from DNA sequence for complex enzyme superfamilies

点击翻译按钮获取中文摘要

Plants are a rich source of drugs and other useful molecules. Examples include the anticancer drugs taxol (from yew trees) and vinblastine and vincristine (from Madagascan periwinkle); the antimalaria compound artemisinin from wormwood; the sweetener stevioside from sweetleaf; and flavours and fragrances such as menthol and limonene, from mint and citrus, respectively. While the biosynthetic pathways for ~50 plant natural products have been so far characterised, plants are known to make hundreds of thousands of diverse chemicals for which the biosynthetic pathways are unknown. Based on our knowledge of the overall classes of enzymes that we associate with plant natural product biosynthesis it has become clear from studying the sequences of plant genomes that plants have the potential to encode far more chemical diversity than has previously been appreciated. However, although we can identify genes in genome that 'look guilty' because they are predicted to encode enzymes belonging to certain major enzyme classes, this does not tell us exactly what specific chemical transformations these individual enzymes carry out. This project brings expertise in plant natural product pathway discovery and elucidation together with powerful computational approaches to tackle the challenges of decoding the information hidden in plant genomes, deducing the relationship between the structure and function of large enzyme superfamilies, and understanding mechanisms of metabolic diversification in the Plant Kingdom. To achieve this, we will focus on a major class of plant natural products known as the triterpenes, since they are one of the largest and most structurally diverse classes of plant natural products with many health, agronomic and industrial applications.