Pikromycin was the first macrolide antibiotic, isolated in 1951 by the German researchers Brockmann and co-workers from Streptomyces sp. Its structure as a 14-membered lactone linked to D-desosamine was confirmed in 1957. Pikromycin is synthesized through a type I polyketide synthase system in Streptomyces venezuelae. Pikromycin is active against Gram positive bacteria and Mycobacteria. Pikromycin inhibits translation in bacteria by binding to overlapping sites in the ribosomal exit tunnel. Although pikromycin readily arrests the growth of bacteria, ∼40% of cellular proteins continue to be synthesized even at saturating concentrations. Pikromycin is a weak inhibitor of human prolyl endopeptidase.