Deep-learning-enabled antibiotic discovery through molecular de-extinction

Molecular de-extinction aims at resurrecting molecules to solve antibiotic resistance and other present-day biological and biomedical problems. Here we show that deep learning can be used to mine the proteomes of all available extinct organisms for the discovery of antibiotic peptides. We trained ensembles of deep-learning models consisting of a peptide-sequence encoder coupled with neural networks for the prediction of antimicrobial activity and used it to mine 10,311,899 peptides. The models predicted 37,176 sequences with broad-spectrum antimicrobial activity, 11,035 of which were not found in extant organisms. We synthesized 69 peptides and experimentally confirmed their activity against bacterial…

• BA
  Brain and Behavior Research Foundation
• UO
  University of Pennsylvania
• UT
  United Therapeutics Corporation
• IR
  Innovative Research Group Project of the National Natural Science Foundation of China
• NI
  National Institutes of Health

  Awards: -0001, R35GM138201
• DT
  Defense Threat Reduction Agency

  Awards: HDTRA11810041, HDTRA1-23-1-0001, HDTRA1-21-1-0014
• PS
  Perelman School of Medicine, University of Pennsylvania
• NI
  National Institute of General Medical Sciences

  Award: R35GM138201
• NI
  National Institute of Allergy and Infectious Diseases