Improving Drug Discovery From Microorganisms

Abstract

Microorganisms remain unrivalled in their ability to produce bioactive small molecules for drug development. However, the core technologies used to discover microbial natural products have not evolved significantly over the past several decades, resulting in a shortage of new drug leads. Advances in DNA-sequencing and bioinformatics technologies now make it possible to rapidly identify the clusters of genes that encode bioactive compounds and to make computer predictions of chemical structure based on gene sequence information. These structure predictions can be used to identify new chemical entities and provide important physicochemical “handles” that guide compound purification and structure confirmation. Industrialization of this process provides a model for improving the efficiency of natural-product discovery. The application of advanced genomics and bioinformatics technologies is now poised to revolutionize natural-product discovery and lead a renaissance of interest in microorganisms as a source of bioactive compounds for drug development.