Monomer screening for sequence defined polymerization in a genetically modified ribosome
Sequence defined polymers, or polymers of a pre-determined length and sequence, are the “Holy Grail” of polymer synthesis. As the physical properties of polymers are highly dependent upon their chemical composition, the wide range of potential applications for sequence defined polymers has yet to be explored. After millions of years of evolution, the ribosome has become a highly efficient polymerization catalyst. In this project, we will work to capitalize on this efficiency to work to create unnatural sequence defined polymers in a genetically modified ribosome. Collaborators in the Jewett group are currently genetically modifying the ribosomal active site to widen the library of chemistries the ribosome is able to catalyze, while we are exploring the chemistries of monomers that could be polymerized by a genetically modified ribosome. This thesis will first identify monomers capable of polymerization under the restricted conditions set by the ribosome, followed by synthesis of promising monomers, and finally taking steps towards loading the synthesized monomers onto tRNA.