CAREER: The Metabolism of Prenylated Benzoquinones through the Lens of Plant-Prokaryote Phylogenomics

科学价值：本项目旨在阐明萜类醌生物合成网络的结构和进化。远不是坊间流传的化合物，烯酰化醌偶联物是电子和质子转移链的关键辅因子，而电子和质子转移链是我们星球上生物能源生产系统的核心。这包括光合作用、呼吸作用和化学合成，仅举几例。但是，由于醌的含量很少，而且在大多数生物体中，它们的同源生物合成突变体是致命的，因此醌很难研究，醌代谢的一些最重要的分支仍然未知。在传统的生化和遗传方法遇到瓶颈的地方，本研究利用了一种系统生物学替代方法，将比较基因组推断与计算机代谢重建相结合，因此候选基因可以通过反向遗传学、酶学研究和靶向代谢物分析来识别和实验测试。植物特别适合这种类型的整合方法，因为它们的基因组已经被“丰富”，通过大量的横向基因转移事件，直接来自细菌和古细菌的基因。更广泛的影响：该项目将为学生和教师建立一个在线资源，以促进全国生物信息学数据挖掘的学习。基于主动学习方法，个人作业和持续评估，该项目将教会学生在他们当前和未来的研究中充分利用系统基因组学方法。该项目还将通过针对中学年龄儿童的一揽子教育方案提高对维生素营养的认识，对这些儿童强调植物微量营养素和良好饮食习惯的重要性。此外，本项目亦将资助学院实验室培养两名本科生研究助理、一名博士生及一名博士后。

Scientific merit: This project aims to elucidate the architecture and evolution of the biosynthetic networks of terpenoid quinones. Far from being anecdotal compounds, prenylated quinone conjugates are key cofactors for the electron and proton transfer chains that are at the core of the bio-energy production systems on our planet. This includes photosynthesis, respiration, and chemosynthesis, just to name a few. But because quinones are present in trace quantities and in most organisms their cognate biosynthetic mutants are lethal, quinones are difficult to study and some of the most important branches of quinone metabolism are still uncharted. Where conventional biochemical and genetic approaches have hit a wall, this research makes use of a system biology alternative that combines comparative genomic inferences with in silico metabolic reconstructions, so candidate genes can be identified and experimentally tested by means of reverse genetics, enzymological studies and targeted metabolite profiling. Plants are particularly well suited for this type of integrative approach, for their genomes have been 'enriched', via numerous events of lateral gene transfer, in genes of direct bacterial and archaeal origin.Broader impacts: This project will establish an on-line resource for both students and instructors in order to promote the learning of bioinformatics data mining nationwide. Based on active learning methods, personal assignments, and continuous evaluation, the project will teach students to get the full benefit of phylogenomics methods for their current and future research. The project will also raise awareness of vitamins nutrition through an educational package aimed at children of middle school age, for whom it highlights the importance of plant micronutrients and good dietary habits. The project will also contribute to the training of two undergraduate research assistants, one PhD student, and one postdoctoral associate in the laboratory of the PI.