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.

在结构上是最多样化的天然产物，具有超过40,000种已知化合物。萜烯合酶和氧化酶的配位生化反应[例如，细胞色素P450单加氧酶（P450）]催化了简单的先前分子中的植物中植物中独特功能化（氧化的）萜烯骨链的合成，是异源性分子的，是同烯基苯甲酸酯。萜类化合物的巨大多样性是自然界中适应性酶演变的结果。为了理解自适应酶的演化，化学多样化及其对植物生态拟合性的影响，我建议研究葵花籽（星芦科或compositae）家族中的萜类化代谢作为模型系统。大约5000万年前，Asteraceae家族中的植物首先出现在南美，一种特征性的萜类化合物（称为倍半萜烯内酯）在不同环境中的大量星形植物的大量物种形成。该提案中的一个特定重点是研究素，生菜和相关的星曲植物物种的倍半萜内代谢，从酶进化和化学多样化的角度研究。以下列出的四个目标将从本提案中实现。比较基因组学和代谢工程工具将用于阐明葵花籽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代谢的细胞配位。受星际科家族中鉴定出的古代P450的先天底物滥交的启发，P450酶工程将尝试通过通过理性设计创建具有新颖的催化功能的人造P450酶。倍半萜内酯的立体化学变体对抗星际科植物防御昆虫的防御的影响将通过分子方法评估。从这些综合方法获得的数据将使我们能够增强对植物酶的进化和化学多样化的了解，并设计改进的酶设计和植物防御的分子策略。