Since the late 20th century, the prevalence of infectious diseases caused by the drug-resistant bacteria, especially by the Gram-positive ones has become a serious problem in the medical treatments, rendering the major antimicrobial drugs less active or ineffective against many important bacterial infections1,2). Thus the newer drugs effective against the multidrug-resistant bacteria are being requested.Recently, we have discovered novel compounds designated tripropeptins (TPPs); particularly tripropeptin C (TPPC) and tripropeptin D (TPPD) show the excellent activities against Gram-positive bacteria including both methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE)3). The antimicrobial activities of these tripropeptins correlate well to the length of fatty acyl side-chains, indicating that the longer was the more active3). Thus, we are greatly interested in the study on the structure-activity relationship regarding fatty acyl side-chains.The present paper described the isolation of a new type of tripropeptin-antibiotic, tripropeptin E (TPPE), its chemical and physicochemical characterization and also its anti-bacterial activities. Furthermore, the structure-activity relationship of tripropeptin-like lipopeptides will be discussed.