Rockefeller University researchers have pioneered terabase-scale long-read sequencing of soil metagenomes to unveil novel bioactive molecules, including two new antibiotic leads. This culture-independent approach leverages large DNA fragment assembly to access previously hidden microbial diversity beyond traditional cultivation methods. The method offers a scalable avenue for antibiotic discovery amidst rising resistance. The findings spotlight the soil microbiome’s vast untapped potential as a drug discovery reservoir.