The B Vitamin/Cofactor Network: Command and Control of Metabolism in Changing Conditions

PI：安德鲁·汉森（佛罗里达大学盖恩斯维尔分校）共同PI：克里斯托弗·亨利（芝加哥大学），唐纳德·麦卡蒂和杰西·格雷戈里（佛罗里达大学盖恩斯维尔分校）主要合作者：阿利斯代尔·弗尼（德国戈姆马克斯·普朗克研究所）和斯维特拉娜·格德斯（阿贡国家实验室）植物和人类一样需要B族维生素，但与人类不同的是，植物自己制造维生素。然而，有一种假设认为，当植物暴露在高温、干旱或其他气候压力下时，它们无法制造所需的所有B族维生素，由此产生的维生素缺乏会导致代谢缺陷，从而导致产量和活力下降。利用玉米，该项目将利用尖端的遗传、基因组和代谢计算机建模方法来验证这一假设，即确定气候胁迫对代谢的影响程度是由于B族维生素缺乏。潜在的结果包括为理解应激代谢和适应气候应激的育种提供新的范例，以及鉴定提高应激适应的特定基因。在推广和培训方面，该项目将提供研究培训活动，使研究人员能够掌握基因组规模的代谢模型。除了培养博士后助理和学生外，该项目还将每年举办一次代谢建模和比较基因组学研讨会，以培养教师、博士后和学生，重点是来自少数民族服务机构的学生。B族维生素形成一个网络。过去的研究表明，这一网络受到气候胁迫的严重影响，由此导致的维生素缺乏导致植物表现不佳。然而，压力导致B族维生素缺乏这一令人惊讶的观点从未经过严格的测试。也没有系统地定义B族维生素在植物中的代谢后果。这个项目将使用以玉米为模型的代谢系统方法来做这两件事。它还将通过识别“缺失的”转运体和酶来填补维生素B网络的关键空白。项目目标是建立一个缺乏维生素b的玉米品系小组，并获得转录组和代谢组数据；建立代谢模型，首次在植物中将所有B族维生素/辅助因子作为工作部分，并利用它们来预测维生素缺乏如何影响叶片代谢和基因表达；通过比较气候压力和维生素缺乏转录组和代谢组来预测压力引起的维生素缺乏症，并通过提供维生素来验证预测；并且，从转录组数据和建模中确定候选转运体和酶基因，对其进行生化和遗传验证，并通过添加它们来升级模型。该研究将为了解B族维生素缺乏如何影响植物基因表达和代谢提供新的视角，从而为胁迫代谢的操纵和代谢适应气候胁迫的育种提供新的见解。所有基因组规模的数据集将在PlantSEED （http://plantseed.theseed.org/）和GEO （www.ncbi.nlm.nih.gov/geo/）上公开。该项目的注释、代谢重建和建模功能也将在PlantSEED中公开，并将用于支持Gramene、iPlant协作以及AraCyc、MaizeCyc和PlantCyc数据库。维生素缺乏玉米品系将成为研究B族维生素及其与微生物群交换的独特资源，并将通过玉米遗传合作库存中心向公众提供。

PI: Andrew Hanson (University of Florida-Gainesville)Co-PIs: Christopher Henry (University of Chicago), Donald McCarty and Jesse Gregory (University of Florida-Gainesville)Key Collaborators: Alisdair Fernie (Max Planck Institute, Golm, Germany) and Svetlana Gerdes (Argonne National Laboratory)Plants need B vitamins just as much as humans do but, unlike humans, plants make their own vitamins. However, it has been hypothesized that plants can fail to make all the B vitamins they need when exposed to heat, drought, or other climatic stresses, and that the resulting vitamin deficiencies cause metabolic defects leading to yield and vigor losses. Using maize, this project will exploit cutting-edge genetic, genomic, and metabolic computer modeling approaches to test this hypothesis, i.e. to determine the extent to which climatic stress effects on metabolism are due to B vitamin deficiency. Potential outcomes include the provision of a new paradigm for understanding stress metabolism and breeding for adaptation to climate stress, and the identification of specific genes to improve stress adaptation. With regard to outreach and training, the project will provide for research training activities that will put genome-scale metabolic modeling in researchers' hands. In addition to the training of postdoctoral associates and students, the project will hold a yearly workshop in metabolic modeling and comparative genomics to train faculty, postdoctorals, and students with an emphasis on those from Minority-serving Institutions. B Vitamins form a network. Past studies imply that this network is severely impacted by climatic stresses and that the resulting vitamin deficiencies lead to plant underperformance. However the surprising idea that stresses cause B vitamin deficiencies has never been rigorously tested. Nor have the metabolic consequences of B vitamin depletion in plants been systematically defined. This project will do both using a metabolic systems approach with maize as a model. It will also fill crucial gaps in the B vitamin network by identifying 'missing' transporters and enzymes. Project objectives are to create a panel of vitamin B-deficient maize lines and acquire transcriptome and metabolome data; build metabolic models that - for the first time in plants - will include all B vitamins/cofactors as working parts and use them to predict how vitamin deficiency affects leaf metabolism and gene expression; predict stress-induced vitamin deficiency by comparing climate-stress and vitamin-deficiency transcriptomes and metabolomes, and validate predictions by supplying vitamins; and, identify candidate transporter and enzyme genes from transcriptome data and modeling, validate them biochemically and genetically, and upgrade the model by adding them. This research will inform perspectives on how B vitamin deficiency impacts plant gene expression and metabolism and in so doing, provide new insight into the manipulation of stress metabolism and breeding for metabolic adaptation to climate stress. All genome-scale datasets will be publicly available at PlantSEED (http://plantseed.theseed.org/) and GEO (www.ncbi.nlm.nih.gov/geo/). The project's annotation, metabolic reconstruction, and modeling capabilities will also be publicly available in PlantSEED and will be leveraged to support Gramene, the iPlant Collaborative, and the AraCyc, MaizeCyc, and PlantCyc databases. Vitamin-deficient maize lines will be a unique resource to study B vitamins and their exchange with the microbiome, and will be made publicly available via the Maize Genetics Cooperation Stock Center.