► The fungal secondary metabolite Cladosporin inhibits liver- and blood-stage malaria parasites ► Cladosporin specifically targets lysyl-tRNA synthetase (Krs1) ► Cladosporin is >100-fold more potent against parasite Krs1 relative to the human enzyme ► Two amino acids in the Krs1 ATP-binding pocket confer species-selective inhibition. The gene discussed is KARS1; the disease is malaria.