How to discover new antibiotics: harvesting the parvome

Abstract

There is a dire need for new antibiotics; commercial discovery programs have essentially dried up and there is talk of 'a return to the pre-antibiotic era'. Natural products are an inexhaustible source of bioactive compounds (antibiotics among them), and recent technical advances such as DNA sequencing and bioinformatics offer new approaches to small molecule discovery. Given that nucleotide sequence studies of actinomycetes genomes reveal the presence of 20 or more pathways for the synthesis of bioactive compounds, 'mining' these sequences offers the potential of expanding the repertoire of antibiotics and other drugs. Combined with advanced chemical separation and characterization techniques, the construction of large chemically diverse libraries of bioactive compounds for therapeutic applications is a realistic near-term goal.