Chemoenzymatic Synthesis of Darobactin A and Analogs

Project Description

Darobactin A is, a new natural product that selectively targets Gram-negative bacteria, it was recently isolated from Photorhabdus bacteria living within the digestive system of nematodes. In this project, we aim to develop a scalable, chemoenzymatic synthesis of darobactin A and analogs by assembling darobactin pro-peptides and studying their oxidative processing with DarE. In efforts to carry out the project goals we will synthesize a library of N-protected 10-mers containing Trp, Lys, and Ser structural analogs. Additionally, we plan to synthetically cleave N-terminal protecting groups and structurally elucidate the product via NMR and MicroED. We plan to generate various analogs that will be subjected to antimicrobial assays to study antibiotic activity which could give rise to a new series of drug candidates to target gram negative pathogens.

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