For over a century, the hunt for new antibiotics has focused almost exclusively on bacteria and fungi. Today, that paradigm shifts. By coupling state-of-the-art AI with the vast, largely uncharted diversity of Archaea, we open a new frontier for molecular discovery. Our APEX model sifted through hundreds of archaeal proteomes in silico, revealing a previously hidden family of antimicrobial peptides we call “archaeasins.” Of the 80 candidates we synthesized, 93% were active against pathogenic microbes in vitro, and one—archaeasin-73—matched the in-vivo efficacy of last-resort drugs such as polymyxin B. These results show that the marriage of deep learning and evolutionary diversity can surface potent therapeutics at digital speed, expanding the antibiotic toolbox when humanity needs it most. Archaea, once thought biologically esoteric, now stand alongside bacteria and fungi as a rich reservoir of useful molecules. We are excited to keep discovering antibiotics at digital speed with AI. Link to the paper @NatureMicrobiol @NaturePortfolio: nature.com/articles/s41564-0…