The objective of this proposal is to create a new paradigm for metabolic pathway optimization through dynamic regulation of pathway expression. This will be done as a GOALI partnership with Manus Biosynthesis (Manus Bio) by developing a new class of regulatory elements called synthetic inducible feedback promoters (IFPs) that combine gene expression timing control with dynamic stress response feedback. We will engage and inform the public about the potential of biomanufacturing for benefiting society and the challenges to achieving the field’s promise by a three-part broader outreach plan that integrates with this research. These activities are geared toward three distinct communities including high school students, the Maker Faire “makers” and do-it-yourself biology (DiY bio) communities. Advances in metabolic engineering and synthetic biology gave rise to a new biomanufacturing economy that promises to transform the way fuels, chemicals, and medicines are produced. However, engineered metabolic pathways impose burden on biomanufacturing hosts causing loss of pathway productivity, and companies that enter the field (such as GOALI partners at Manus Bio), must overcome this critical challenge. Hence, companies expend great resources to search for genetic optimizations that balance pathway expression with host burden. These optimizations are often costly in terms of time and money and too specific to be broadly applicable to different pathways and products. To address this challenge, the PI’s propose IFPs that interface stress responsive feedback promoters with inducible timing control using RNA regulators. IFPs represent a new regulatory concept for metabolic pathway control and optimization: inducibility allows titration and timing of pathway expression to be rapidly explored, while stress responsive feedback allows autonomous expression optimization. The central objective of this proposal is to develop and validate IFPs in the context of two industrially important, yet different, metabolic pathways: terpenoid oxygenation (a critical technology for Manus Bio) and n-butanol production. This objective will be pursued in aims that validate the approach of IFP regulation, create a public resource of unique IFPs applicable to many different metabolic pathways, and fine-tune IFPs that are directly applicable for use by industry in large-scale bioprocesses.
|Effective start/end date||9/1/18 → 8/31/23|
- National Science Foundation (CBET-1803747)
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