Rescuing Auxotrophic Microorganisms with Nonenzymatic Chemistry

摘要

Chemical manipulations of small-molecule metabolites take place in all living systems and are essential for sustaining life through cellular metabolism. The vast majority of these transformations are carried out by macromolecular, enzymatic catalysts. In contrast to the natural world, most chemical reactions employed in laboratory syntheses utilize nonbiological reagents and catalysts Although nonbiolog-ical catalysts and reagents have been shown to function in the presence of cells the question of whether or not their reactivity can interface with cellular metabolism and influence biological function remains/underexplored. We are interested in further developing-' this aspect of reaction methodology, which we term biocompatible chemistry: nonenzymatic chemical transformations that can be used to manipulate the structures of small molecules in the presence of living organisms. Successful integration of biocompatible chemistry with cellular metabolism would have implications for biotechnology, because it could expand the capabilities of biotransformation in ways that are not possible using enzymes. Establishing a link between nonenzymatic catalysis and metabolism could also have potential implications for prebiotic chemistry, because it would suggest that primitive cells could have relied upon nonenzymatic transformations occurring in the surrounding environment to generate essential metabolites.Here, we describe biocompatible chemical reactions that interact with microbial metabolism and rescue auxotrophy through the production of essential metabolites. This experimental approach enables us to directly connect the growth of a living organism to the success of a nonbiological chemical transformation.