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In Vivo Metabolite Modification in Hybrid Biological and Chemical Synthesis Systems (IVMMHBCSS)
Start date: Mar 1, 2014, End date: Feb 28, 2017 PROJECT  FINISHED 

"This proposal aims to integrate the fields of synthetic biology and synthetic organic chemistry. This project aims to achieve this through the application of biocompatible chemistry: non-enzymatic reactions capable of modifying small molecules in the presence of a living system. The idea of using microbial metabolites as reagents for non-enzymatic transformations in the presence of the producing organism will greatly expand the range of organic molecules that can be accessed using natural and engineered living systems.We plan on applying a newly discovered engineered strain of E.coli that produces molecular hydrogen to important synthetic targets. We have demonstrated the use of this microbe in the presence of a palladium catalyst to hydrogenate a range of alkene- and alkyne-containing unnatural substrates. We propose to use this biocompatible hydrogenation reaction to the synthesis of industrially important advanced biofuels from biologically available starting materials. This would avoid the current need to extract the products of an engineered organism for further chemical manipulations, and would be the first example of the synthesis of these proposed molecules through purely biological means. Using bacterial olefin biosynthesis for the production of alkanes by interfacing single-/multi-system bacterial metabolism and a non-enzymatic, biocompatible hydrogenation reaction will represent an important advance in metabolic engineering and in biofuel manufacture.We then plan to develop a batch- or flow-reactor set-up in order to investigate the viability of advanced biofuel synthesis using an engineered microbe/non-enzymatic chemistry synthesis systems for the bulk production of these important target molecules."
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