Investigating isoprenoid metabolism in the sunflower (Asteraceae) family

研究向日葵（菊科）家族的类异戊二烯代谢

• 批准号: 341655-2012
• 负责人: Ro, DaeKyun
• 金额: $ 3.42万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=595456
• 关键词: Investigating; isoprenoid; metabolism; sunflower; Asteraceae

Terpenoids (or isoprenoids) are structurally the most diverse natural products with more than 40,000 known compounds. Coordinated biochemical reactions of terpene synthase and oxidase enzymes [e.g., cytochrome P450 monooxygenase (P450)] catalyze the synthesis of uniquely functionalized (oxidized) terpene backbones in plants from a simple precursor molecule, isopentenyl diphosphate. The enormous diversity of terpenoids is the outcomes of adaptive enzyme evolutions in nature. In order to understand the adaptive enzyme evolution, chemical diversification, and its influence on the plant eco-fitness, I propose to investigate the terpenoid metabolism in the sunflower (Asteraceae or Compositae) family as a model system. Plants in the Asteraceae family first emerged in the South America about 50 million years ago, and a characteristic sub-class of terpenoid, called sesquiterpene lactone, has diversified alongside the massive speciation of the Asteraceae plants in distinct environments. A specific focus in this proposal is to study sesquiterpene lactone metabolism in sunflower, lettuce and related Asteraceae plant species from the perspectives of enzyme evolution and chemical diversification. Four objectives listed below will be achieved from this proposal. Comparative genomics and metabolic engineering tools will be used to elucidate the details of the sesquiterpene lactone biochemistry in sunflower and lettuce; Metabolic and/or protein trafficking among different cell types will be investigated to understand the cellular coordination of terpenoid metabolisms in lettuce; Inspired by the innate substrate promiscuity of ancient P450s identified in Asteraceae family, P450 enzyme engineering will be attempted to create a pool of artificial P450 enzymes with novel catalytic functions by rational design; The impact of stereo-chemical variants of sesquiterpene lactone on the defense of the Asteraceae plant against insects will be assessed by molecular methods. The data obtained from these integrative approaches will enable us to enhance our knowledge of the plant enzyme evolution and chemical diversification and to devise the improved molecular strategies for enzyme design and plant defense.

萜类化合物（或类异戊二烯）是结构最多样化的天然产物，已知化合物超过 40,000 种。萜烯合酶和氧化酶 [例如细胞色素 P450 单加氧酶 (P450)] 的协调生化反应催化植物中从简单的前体分子异戊烯基二磷酸合成独特功能化（氧化）的萜烯主链。萜类化合物的巨大多样性是自然界适应性酶进化的结果。为了了解适应性酶的进化、化学多样化及其对植物生态适应性的影响，我建议以向日葵（菊科或菊科）家族作为模型系统来研究萜类化合物代谢。菊科植物大约 5000 万年前首次出现在南美洲，萜类化合物的一个特有子类（称为倍半萜内酯）随着菊科植物在不同环境中的大量物种形成而多样化。该提案的一个具体重点是从酶进化和化学多样化的角度研究向日葵、生菜和相关菊科植物物种中的倍半萜内酯代谢。该提案将实现以下四个目标。比较基因组学和代谢工程工具将用于阐明向日葵和生菜中倍半萜内酯生物化学的细节；将研究不同细胞类型之间的代谢和/或蛋白质运输，以了解生菜中萜类化合物代谢的细胞协调；受菊科古代P450先天底物混杂性的启发，P450酶工程将尝试通过合理设计创建具有新颖催化功能的人工P450酶库；将通过分子方法评估倍半萜内酯的立体化学变体对菊科植物防御昆虫的影响。从这些综合方法中获得的数据将使我们能够增强对植物酶进化和化学多样化的了解，并设计出改进的酶设计和植物防御分子策略。