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

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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.