Project Description

Visit the Synthesizers' stand during Giant Jamboree! Get tuned in and listen to our podcast explaining our project!

Figure 1

Non-ribosomal peptides have important anti-bacterial, anti-cancer, and immunosuppressive biological activities. They are synthesized by modular, high molecular weight enzymes that assemble more than 500 different amino acid substrates in an assembly line manner. For this reason, synthetic biologists have tried to engineer these proteins and to switch modules to create analogs and novel natural products, but with little success. Despite being modular, the interactions between modules have evolved to be highly specific, making synthetic Non-Ribosomal Peptide Synthases (NRPS) a challenge to engineer. Instead of switching modules we introduced a recombination system targeting oligo integration in Bacillus subtilis. We used the recombineering system to alter the active sites determining substrate specificity, thereby creating variants of antibiotics. Our focus was the tyrocidine antibiotic, which cannot be used intravenously due to its toxicity. Our goal is to create new analogs through multiplex automated genome engineering to reduce toxicity.

Social Media