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(6az) Engineering Cell Metabolism for Better Health, Safe Environment and Efficient Fuels

Authors: 
Xu, P., MIT
Koffas, M. A. G., Rensselaer Polytechnic Institute
Stephanopoulos, G. N., Massachusetts Institute of Technology

The diversity and richness of cell metabolism provides us with enormous opportunity to implement sustainability and make this world a better place. However, the complexity underlying natural biological systems restrained our ability for targeted manipulation and optimal control of cell metabolism. To bridge this gap, synthetic biology has emerged aiming at development of novel tools that support the design, construction and control of cell metabolism and maximize the performance of the engineered cell.  Undoubtedly, cell metabolism engineering is going to address some of the critical challenges facing the human kind and will provide us novel solutions for the treatment of complex diseases and sustainable production of fuels and green chemicals.

Despite the development of advanced cloning and gene assembly platforms, we are still limited by the speed and scales at which we can engineer microbes before we can realize the full potenital of cell metabolism. To address this challenge, multiplexed combinatorial pathway engineering coupled with regulatory elements evolution will allow us to rapidly optimize the efficiency of a specified pathway. As one of the promising approaches, I will engineer synthetic regulatory RNAs to post-transcriptionally and translationally modulate gene expression and improve pathway efficiency. Other challenge in cellular engineering is to engineer smart cells that integrate metabolite-sensing genetic cirucits with the physiological states of cell and achieve self-adaption.  Cellular resources (NADPH or ATP) will be autonomoulsy partitioned to either cell growth pathway or metabolite production pathway depending on the state of the cell. To achieve these goals, I will engineer metabolite bio-sensors, valves, transporters and controllers that integrate both negative feedback control and positive feed-forward control to improve the production of therapeutical or fuel molecules.

I am fascinated and excited by the possibilities that metabolic engineering and synthetic biology have afforded to transform the world and improve our life. I am particularly interested in applying my knowledge and expertise to engineer human gut microbiota for self-tuning therapeutics and diagnostics; engineer microorganisms for cost-efficient production of pharmaceuticals, green chemicals and fuel molecules; develop synthetic biology tools that facilitate cell metabolism evolution and optimization; integrate synthetic feedback control and metabolic circuits to improve therapeutic and pathway efficiency. Taken together, these strategies will allow us to rapidly interrogate and control cell metabolism and develop innovative sustainable solutions to upgrade low-value carbons to high-value therapeutics or green chemicals.


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