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

植物是药物和其他有用分子的丰富来源。例子包括抗癌药物紫杉醇（紫杉树）和长春碱和长春新碱（从长春花）;抗疟疾化合物青蒿素从艾草;甜菊糖甜菊苷从甜叶;和香料和芳香剂，如薄荷醇和柠檬烯，分别从薄荷和柑橘。虽然到目前为止已经确定了约50种植物天然产物的生物合成途径，但已知植物会产生数十万种生物合成途径未知的不同化学物质。基于我们对与植物天然产物生物合成相关的酶的全部类别的知识，通过研究植物基因组的序列已经清楚地表明，植物具有编码比以前认识到的多得多的化学多样性的潜力。然而，尽管我们可以识别基因组中“看起来有罪”的基因，因为它们被预测编码属于某些主要酶类别的酶，但这并不能确切地告诉我们这些酶进行了哪些特定的化学转化。该项目将植物天然产物途径发现和阐明方面的专业知识与强大的计算方法结合在一起，以应对解码隐藏在植物基因组中的信息，推导大型酶超家族的结构和功能之间的关系以及理解植物王国代谢多样化机制的挑战。为了实现这一目标，我们将专注于一个主要类别的植物天然产物被称为三萜类，因为它们是最大的和结构上最多样化的植物天然产物类别之一，具有许多健康，农学和工业应用。

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.