CAREER: Engineered Protein Complexes for Designable Control over Metabolic Pathway Flux

微生物可以通过新的和/或修改的代谢途径来制造各种各样的化合物，包括香料和芳香剂，治疗剂，塑料和生物燃料。该项目旨在研究活细胞内的工程蛋白质组装体可以改善这些理想化学品的可持续生产的方式。支架蛋白组装体是使用模块化蛋白质-蛋白质相互作用部分构建的，其作用是共同定位给定途径的酶，形成更有效地催化生产中涉及的化学反应的复杂结构。模块化部件的使用提供了对结构的可编程控制，尽管目前产品形成的变化是不可预测的。然而，该系统的模块化性质将允许对关键架构特征进行轻松操作，以测试假设并确定功能组装和提高产量的关键设计原则。了解蛋白质支架及其对生产的影响的基本规则，应大大提高我们的能力，将这一战略应用于新的途径和products.Broader影响外联活动已被设计为介绍合成生物学研究更广泛的教育界。国际基因工程机器（iGEM）竞赛将成为核心推广平台。这个一年一度的暑期项目将涉及伯克利大学本科生，未来的社区大学转学生，以及在职和职前高中教师。该团队将在合成生物学实验室中得到密集的同行和高级导师的指导;因此，在完成后，他们将被赋予进行独立研究的能力。更多的学生将通过参与的高中教师间接受到影响，他们将利用自己在该计划中的经验更好地指导学生，激发和培养对科学和工程职业的兴趣。

AbstractMicrobes can be engineered with new and/or modified metabolic pathways to make a wide variety of compounds, including flavors and fragrances, therapeutics, plastics, and biofuels. This project aims to investigate the manner in which engineered protein assemblies within living cells can improve the sustainable production of these desirable chemicals. Scaffolded protein assemblies are built using modular protein-protein interaction parts, which act to co-localize enzymes of a given pathway, forming a complex structure that more efficiently catalyzes the chemical reactions involved in production. The use of modular parts provides programmable control over the structure, though currently the resulting changes in product formation are not predictable. However, the modular nature of this system will allow for facile manipulation of key architectural features to test hypotheses and determine the critical design principles for functional assembly and increased production. Understanding the fundamental rules governing protein scaffolding and its effects on production should considerably improve our ability to apply this strategy to new pathways and products.Broader impactsOutreach activities have been designed to introduce synthetic biology research to the broader educational community. The international Genetically Engineered Machines (iGEM) competition will be the core outreach platform. This annual summer-long program will involve a team of Berkeley undergraduates, prospective community college transfers, and both an in- and a pre-service high school teacher. The team will be guided by intensive peer and senior mentorship in a working synthetic biology lab; thus upon completion they will be empowered with the ability to conduct independent research. A far greater number of students will be indirectly influenced through the participating high school teachers, who will use their experiences in the program to better mentor their students and inspire and nurture interest in careers in science and engineering.