S10: Genomic approaches for discovery of phosphonic acid antibiotics

Phosphonic acids, organic molecules containing direct carbon-phosphorus bonds, represent a potent, yet underexploited, group of compounds with great promise in the treatment of human disease. Numerous, structurally distinct, phosphonates are produced in nature and many have useful bioactive properties. Despite their utility, little is known about the biosynthesis of these natural products. In recent years, we have employed a gene-based strategy to identify organisms with the capacity to produce phosphonic acid natural products. These studies have identified the biosynthetic gene clusters responsible for biosynthesis of numerous bioactive phosphonates, including ones clinically used as antibacterial, antiviral, antifungal and antimalarial agents. Our approach has also led to the discovery of several promising new antibiotic compounds. Finally, our studies indicate that phosphonate biosynthesis is common in the microbial world and suggest that the role of phosphonic acids in the biosphere may have been grossly underestimated.