Zelkovamycin

Zelkovamycin is a cyclic octapeptide antibiotic isolated from Streptomyces sp. K96-0670 and structurally characterized as a thiazole- and tryptophan-containing macrocycle. Subsequent total synthesis and structural revision established zelkovamycin as a member of the argyrin natural product family. Biological investigations demonstrated that zelkovamycin uniquely inhibits oxidative phosphorylation (OXPHOS), distinguishing it from other argyrins and positioning it as a chemical probe for mitochondrial respiration. In addition to OXPHOS inhibition, zelkovamycin exhibits antibacterial activity against plant and Gram-positive pathogens and has inspired analogue synthesis for anticancer evaluation. These findings define zelkovamycin as an OXPHOS-inhibitory cyclic peptide natural product within the argyrin family.