adep1

ADEP1 is a **natural product antibiotic** and the prototypical member of a new class of antibiotics known as **acyldepsipeptides (ADEPs)**, produced by *Streptomyces hawaiiensis* NRRL 15010 as part of the A54556 antibiotic complex[1][5]. Its structure features a macrolactone core of five amino acids cyclized by a depsipeptide bond and an *N*-acylated L-phenylalanine polyene side chain, with a noncanonical (2S,4R)-4-methylproline residue critical for its high antibacterial activity[1][5]. Mechanistically, ADEP1 activates the **caseinolytic protease ClpP**, converting it from a tightly regulated bacterial protease into an unregulated protein-degrading machine, which leads to uncontrolled degradation of essential bacterial proteins, such as FtsZ, causing bacterial cell death[3][5][7][8]. ADEP1 demonstrates significant **bactericidal activity**, particularly against Gram-positive bacteria (including methicillin-resistant *Staphylococcus aureus* (MRSA), vancomycin-resistant *Enterococcus* (VRE), and penicillin-resistant *Streptococcus pneumoniae*), and is active not only against growing bacteria but also against dormant and biofilm states[5][8]. ADEP1 is primarily a research compound and serves as the lead molecule for developing improved synthetic ADEP antibiotics with enhanced stability and pharmacological properties[5][8].

Other names

acyldepsipeptide 1acyldepsipeptide1acyldepsipeptide-1factor Aadep antibiotic a54556 factor a