<jats:p>Three new polyketides, lactomycins A (1)–C (3), were isolated from the culture broth of a marine-derived Streptomyces sp. ACT232 as cathepsin B inhibitors. Their structures were determined by a combination of NMR and MS data analyses to be the dephosphorylated derivatives of a phoslactomycin class of metabolites. Lactomycins exhibited cathepsin B inhibitory activity (IC50 0.8 to 4.5 μg/mL). Even though the biosynthetic gene clusters found in the genome of the current strain have high similarity to those of phoslactomycin, neither phoslactomycins nor leustroducsins were detected by LC-MS analyses of the crude extract.