β-lactone natural products are chemical compounds characterized by strained four-membered rings that act as potent enzyme inhibitors. β-lactone synthetases are enzymes that utilize ATP to drive intramolecular ring closure and subsequent β-lactone formation and represent an attractive route to asymmetric synthesis of medically relevant β-lactones, particularly against tuberculosis. However, currently there are no crystal structures of stand-alone β-lactone synthetases and very limited kinetic data. The focus of this project was to identify, recombinantly express, and characterize various β-lactone synthetases from ten different bacteria from around the world. Multiple active enzymes were found with<i> Stenotrophomonas pavanii</i>, displaying particularly good results upon further characterization. Finally, a 96-well plate screen for the generation of bioactive beta-lactones by these enzymes was created and used as a proof of principle experiment.

Expression and characterization of taxonomically diverse β-lactone synthetases for chemoenzymatic synthesis

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.