Abstract - Phosphonic acids are a class of natural products with significant potential for utility in medicine and biotechnology. Underlying the antibiotic, herbicidal, and antiviral activity of many phosphonic acid natural products is their mimicry of cellular phosphate esters and carboxylic acids to inhibit essential metabolic pathways. Although genomics illuminates a growing trove of thousands of gene clusters suggestive of novel phosphonic acids across all microbial taxa, accurate de novo forecasting of their chemical products and inhibitory properties to prioritize discovery is precluded by our nascent understanding of their biosynthetic diversity. In search of methods to improve genomics-enabled discovery of phosphonic acids, my research group seeks to understand universal physiological and biochemical principles underlying the chemical diversity of these natural products. The seminar will describe our efforts to expand and refine the framework of phosphonic acid natural product genomics by the isolation of new compounds from cryptic gene clusters and the discovery of new pathways and enzymes for their biosynthesis.