Actinonin is a peptidomimetic antibiotic produced by Actinomyces that inhibits aminopeptidases. It inhibits the following matrix metalloproteinases (MMPs): MMP-1 (Ki = 300 nM), MMP-2 (IC50 = ~90 nM), MMP-3 (Ki = 1,700 nM), MMP-7 (IC50 = ~3,500 nM), MMP-8 (Ki = 130 nM), MMP-9 (Ki = 330 nM), MMP-10 (IC50 = ~500 nM), MMP-12 (IC50 = ~350 nM), and MMP-13 (IC50 = ~100 nM), but not MMP-14 (IC50 > 1 mM). Actinonin acts as an herbicide by targeting plastid peptide deformylase, an enzyme required for N-terminal processing of plastid-encoded proteins. Actinonin has also been identified as an effective inhibitor of human meprin α (Ki = 20 nM), a zinc endopeptidase that cleaves matrix proteins. More recently actinonin has been shown to inhibit tumor cell invasion and matrix degradation and to induce apoptosis in animal models by targeting human mitochondrial peptide deformylase.
