Biosynthesis of genetically encoded biopolymers with abiological monomers

Proteins have essential roles for cells and undertake various functions that are structural, regulatory or catalytic in nature. In the cell, the chemical diversity of proteins are limited to a standard set of 20 L-α-amino acids (L-AA), but there is an interest in enabling non-standard amino acids incorporation into proteins to expand their chemical repertoire and create new types of materials, therapeutics and enzymes. To date, it is not possible to efficiently translate proteins with D-amino acids and building an orthogonal translation system to do so is challenging. Therefore, I seek to perform this project and in doing so gain insight into bacterial translation while creating a path to biosynthesize new types of proteins.

To perform the project, I will start of with chromosomally integrating orthogonal translation components into a genome recoded E. coli strain. Then I will perform extensive mutation and evolution using cutting-edge genome engineering tools such as MAGE to find a strain that can biosynthesize proteins with D-amino acids.