The evolution of shikimate associated metabolic enzymes

莽草酸相关代谢酶的进化

• 批准号: RGPIN-2020-06052
• 负责人: Christendat, Dinesh
• 金额: $ 3.06万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=741001
• 关键词: evolution; shikimate; associated; metabolic; enzymes

In our study, we plan to use structural biology, biochemistry and molecular biology to understand how enzymes of the shikimate pathway have evolved their respective function. Based on this approach, we will functionally annotate classes of proteins whose biological function has not been previously determined. We will target plant and microbial enzymes that stem from the shikimate pathway. There are three main objectives in this proposal: 1) Investigate the evolution of function of SKL1 in chloroplast development. The shikimate pathway plays a central role for the biosynthesis of aromatic compounds in plants and microorganisms. The pathway leads to growth hormones, aromatic amino acids, flavonoids, lignin and other central metabolites in plants. As a result, this pathway is targeted for the development of inhibitors that could function as herbicide or antimicrobial agents. SKL1 is conserved across plant species analyzed, thus the functional annotation of this protein will provide opportunities to engineer crop plants to enhance their photosynthetic efficiency and thus increase their biomass. Inactivating SKL1 directly affects plant growth, therefore an SKL1 inhibitor could function as an effective herbicide. 2) Investigate the biosynthesis and role of Chlorogenic Acids (CGAs) in protecting plants against pathogens. Recently, we functionally annotated proteins involved in CGAs biosynthesis in plants. Although, it was known that plants produce chlorogenic acids, the early steps of the metabolic pathway had not been worked out. CGAs play an important role in our diet, they are powerful antioxidant and are associated with numerous health benefits including aging and protection against cardiovascular diseases. CGAs have powerful antifungal and antifeeding properties, therefore our ability to modulate the accumulation of CGAs at different developmental stages of fruit ripening is economically important. Our studies on CGA biosynthesis in plants will provide opportunities for crop protection. 3) Investigate the role of PCA in facilitating Listeria spp. interaction within the microbiome. We have elucidated the metabolic pathway for the utilization of quinate and shikimate for the production of protocatechuate; it is hypothesized that this compound is used by Listeria species to facilitate their interaction with other organisms in the environment. Decaying green vegetables have high quinate and shikimate content which is implicated in contributing to the growth of Listeria species. We therefore plan to develop strategies to disrupt Listeria interaction with other microorganisms and thus inhibit its ability to contaminate our food sources. The results from these studies will provide a better understanding of this interaction and opportunities to prevent Listeria contamination of food supply.

在我们的研究中，我们计划使用结构生物学，生物化学和分子生物学来了解莽草酸途径的酶如何进化其各自的功能。基于这种方法，我们将在功能上注释其生物学功能尚未确定的蛋白质类。我们将针对植物和微生物酶，从莽草酸途径干。本研究的主要目的有三：1）研究SKL 1在叶绿体发育中的功能演变。 莽草酸途径在植物和微生物中芳香族化合物的生物合成中起着核心作用。该途径导致植物中的生长激素、芳香族氨基酸、类黄酮、木质素和其他中心代谢物。因此，这一途径是开发抑制剂的目标，这些抑制剂可以用作除草剂或抗微生物剂。SKL 1在所分析的植物物种中是保守的，因此该蛋白的功能注释将为工程作物提供机会，以提高其光合效率，从而增加其生物量。使SKL 1失活直接影响植物生长，因此SKL 1抑制剂可以作为有效的除草剂发挥作用。2)研究绿原酸（CGA）的生物合成及其在保护植物免受病原体侵害中的作用。最近，我们对植物中参与CGA生物合成的蛋白质进行了功能注释。虽然，人们知道植物产生绿原酸，代谢途径的早期步骤还没有解决。CGA在我们的饮食中发挥着重要作用，它们是强大的抗氧化剂，具有许多健康益处，包括衰老和预防心血管疾病。CGA具有强大的抗真菌和拒食特性，因此我们能够在果实成熟的不同发育阶段调节CGA的积累具有重要的经济意义。我们对CGA生物合成的研究将为作物保护提供机会。3)调查五氯苯甲醚在促进李斯特菌属中的作用。微生物组内的相互作用。我们已经阐明了利用奎尼酸和莽草酸生产原儿茶酸的代谢途径;据推测，这种化合物被李斯特菌物种用于促进它们与环境中其他生物的相互作用。腐烂的绿色蔬菜具有高的奎尼酸盐和莽草酸盐含量，这与李斯特菌属物种的生长有关。因此，我们计划制定策略来破坏李斯特菌与其他微生物的相互作用，从而抑制其污染我们食物来源的能力。这些研究的结果将使人们更好地了解这种相互作用，并为防止食品供应中的李斯特菌污染提供机会。