Abstract

Significance The discovery of natural products, an important source of human medicines, is critical for the development of new therapeutics against health threats, including cancer and multidrug-resistant pathogens. Yet, in recent years, industrial development of pharmaceuticals from natural products has been stymied due to a variety of reasons, including the repeated discovery of previously known compounds. Here, we demonstrate large-scale genomics as one potential solution to this problem by mining a collection of 10,000 actinomycetes for novel phosphonic acids, an important class of natural products with antimicrobial, antiviral, antimalarial, and herbicidal activities. The framework described here provides a foundation for rapid, large-scale discovery of other classes of natural products and their use as lead compounds in the pharmaceutical industry.