Yeast synthetic biology platform for pathway-level antimicrobial screens

Project Summary Antimicrobial resistance is a global health emergencyDespite thisthe number of new antibiotics in development is limited and there is a desperate need for new pipelines to identify novel antibiotic candidatesWe propose to develop a yeast based drug screening platform to be used in high throughput compound screens to identify molecules with antimicrobial activitytargeting the highest priority pathogensThe overall strategy is to engineer the model organism Saccharomyces cerevisiae so its growth depends on the expression of sets of enzymes transplanted from human pathogensBy introducing entire enzymatic pathwaysfocusing on those that are essential in bacteriafungus and plants but not in humansthe resulting yeast strains will provide an easy system for high throughput drug screening and the opportunity to identify compounds with high therapeutic indicesMoreovereach enzymatic activity in the transplanted pathway will represent a unique druggable targetincreasing the chances of compound identificationThe goal of the Phase I study is to produce a series of engineered yeast strains expressing a pathway with multiple unique enzymatic activitiesfocusing mainly on priority pathogens as identified by the NIAID and the World Health OrganizationOnce developedthese strains can be used in high throughput drug screening studies!Project Narrative We will develop a novel anti infective screening platform by engineering Saccharomyces cerevisiaeyeaststrains to be dependent on enzymatic pathways transplanted from human pathogensThe system will provide a pipeline for high throughput compound screening to identify new antibiotics !