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)合作伙伴：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：Alisdair Fernie(德国高姆马克斯·普朗克研究所)和Svetlana Gerdes(阿贡国家实验室)植物和人类一样需要维生素B，但与人类不同的是，植物可以自己制造维生素。然而，人们假设，当暴露在高温、干旱或其他气候压力下时，植物可能无法产生它们所需的所有B族维生素，由此导致的维生素缺乏会导致代谢缺陷，从而导致产量和活力的损失。以玉米为例，该项目将利用前沿的遗传、基因组和代谢计算机模拟方法来验证这一假说，即确定B维生素缺乏在多大程度上影响气候胁迫对新陈代谢的影响。潜在的成果包括为了解压力代谢和适应气候压力的育种提供了一个新的范式，以及确定了改善压力适应的特定基因。关于外联和培训，该项目将提供研究培训活动，将基因组规模的新陈代谢模型交到研究人员手中。除了培训博士后助理和学生外，该项目还将每年举办代谢建模和比较基因组学研讨会，培训教师、博士后和学生，重点是少数族裔服务机构的学生。维生素B形成了一个网络。过去的研究表明，这一网络受到气候压力的严重影响，由此导致的维生素缺乏导致植物表现不佳。然而，压力会导致维生素B缺乏这一令人惊讶的想法从未经过严格的测试。也没有系统地定义植物体内维生素B耗竭的代谢后果。这个项目将以玉米为模型，使用代谢系统方法来完成这两项工作。它还将通过识别“缺失的”转运蛋白和酶来填补维生素B网络中的关键空白。项目目标是创建一组维生素B缺乏的玉米品系，并获得转录组和代谢组数据；建立代谢模型，首次在植物中包括所有B族维生素/辅因子作为工作部分，并用它们来预测维生素缺乏如何影响叶片代谢和基因表达；通过比较气候胁迫和维生素缺乏的转录体和代谢物来预测胁迫导致的维生素缺乏症，并通过提供维生素来验证预测；以及从转录组数据和建模中确定候选的转运蛋白和酶基因，从生物化学和遗传学上验证它们，并通过添加它们来改进模型。这项研究将为研究维生素B缺乏如何影响植物基因表达和代谢提供新的视角，从而为调控胁迫代谢和育种以适应气候胁迫提供新的见解。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/)上公开提供。该项目的注释、新陈代谢重建和建模能力也将在PlantSEED中公开提供，并将被用于支持Gramene、iPlant Collaborative以及AraCyc、MaizeCyc和PlantCyc数据库。缺乏维生素的玉米品系将是研究维生素B及其与微生物组交换的独特资源，并将通过玉米遗传合作库存中心公开提供。

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.