He is best known for discovering the antibiotic substance penicillin in 1928 . He shared a Nobel Prize in Physiology or Medicine in 1945 for this discovery with Howard Walter Florey and Ernst Boris Chain . His best-known discoveries are the discovery of the enzyme lysozyme in 1923 and the antibiotic substance penicillin from the mold Penicillium notatum in 1928 , for which he shared the Nobel Prize in Physiology or Medicine in 1945 with Howard Florey and Ernst Chain .