An Engineered Pathway for the Green Chemical Synthesis of Beta-lactam Antibiotics
Author: Jerry Sheng
Faculty Supervisor: George Gassner
Department: Chemistry & Biochemistry
The growing prevalence of antibiotic resistant bacteria has called for an increased focus on the development of novel antibiotics as well as facilitating their industrial production. Current methods of synthetic penicillin production are both labor intensive and suffer from equilibrium issues affecting yield, leading consumers to bear a high price tag. Namely, the cost of broad spectrum synthetic penicillins can be as much as 10x for the consumer when compared to natural penicillins. The difficulty in conversion of penicillin G to a series of synthetic penicillins lies in the reacylation of the 6-aminopenicillanic acid (6-APA) antibiotic nucleus. Past research has demonstrated that novel biocatalytic synthetic approaches are beneficial to optimizing medicinal chemistry as well as use of green chemistry. New reaction strategies, continuous product extraction using penicillin G acylases (PGA) with better intrinsic properties have proven to be key to competitive biocatalytic processes in hopes to minimize side reactions. However, the pharmaceutical industry has only focused on this limited enzyme. In our novel research we aim to apply genetic engineering approaches to bridge two separate bacterial pathways for the total synthesis of penicillin derivatives; our enzymatic (AcAldDh/IpnAT) pathway aims to increase yield and reduce cost of production when compared to the current industrial methods.