There is a national objective to replace gasoline, diesel, and plastic materials with biorenewable alternatives that do not compete with our food supply. Engineered micro-organisms can convert sugars into a broad cornucopia of biorenewable products, including fuels and materials. However, the sugar must be very inexpensive to compete with existing petroleum-based products. Non-food agricultural byproducts, such as corn stover and wheat straw, and fast growing trees can be converted to inexpensive sugar through a multi-step biomass conversion process. One of the most challenging aspects of this conversion process is the generation of toxic inhibitors that kill the micro-organism, and thus prevent them from producing a product. In particular, furfural and hydroxy-methyl furfural (HMF) are two of the most toxic inhibitors to micro-organisms.
It is proposed to engineer and optimize a synthetic biodetoxification pathway that enables industrial micro-organisms to consume furfural and hydroxy-methyl furfural, converting them into useful cellular building blocks, and enabling the manufacturing of products using inexpensive cellulosic sugars. This work will also combine furan biosensors with genetic circuitry to automatically tune the pathway's activity in the presence of changing bioreactor conditions. The living cell will only activate the pathway when it needs it. Further, this work will develop new biophysical modeling and computational optimization approaches to make engineering cellular metabolism more efficient and reliable. The proposed model-guided approach will substantially reduce the amount of experimentation that will be necessary to optimize new metabolic pathways, and control their activity according to a metabolite biosensor. New methods will be available through a user-friendly web interface.
The investigator will promote the scholarship and education of high school students, undergraduate students, and graduate students through three targeted programs. The first program will recruit high school teachers to create new design-build-test engineering labs that will demonstrate key engineering principles while illustrating the intersection between biotechnology and our daily lives. In the second program, the PI will enhance the early-stage research opportunities for undergraduate students, especially ones from under-represented groups, as a way to increase graduation rates and encourage the pursuit of higher education. In the third program, the PI will develop a new graduate-level course on Synthetic Biology. This graduate-level course will be a higher-level version of an existing undergraduate course that integrates a genetic, metabolic, and protein engineering curriculum with research topics from the bioenergy and biopharmaceuticals fields.
