• J Mol Cell Cardiol (2020). PMID:33301800

Actinonin is a peptidomimetic antibiotic produced by Actinomyces that inhibits aminopeptidases. It inhibits the following matrix metalloproteinases (MMPs): MMP-1 (Ki = 300 nM), MMP-3 (Ki = 1,700 nM), MMP-8 (Ki = 130 nM), and MMP-9 (Ki = 330 nM).[1] Actinonin acts as an herbicide by targeting plastid peptide deformylase, an enzyme required for N-terminal processing of plastid-encoded proteins.[2] Actinonin has also been identified as an effective inhibitor of human meprin α (Ki = 20 nM), a zinc endopeptidase that cleaves matrix proteins.[3] 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.[4]

Reference:
[1]. Wahl, R.C., Pulvino, T.A., Mathiowetz, A.M., et al. Hydroxamate inhibitors of human gelatinase B (92 kDa). Bioorganic & Medicinal Chemistry Letters 5(4), 349-352 (1995).
[2]. Duke, S.O., and Dayan, F.E. Modes of action of microbially-produced phytotoxins. Toxins (Basel) 3(8), 1038-1064 (2011).
[3]. Kruse, M.N., Becker, C., Lottaz, D., et al. Human meprin α and β homo-oligomers: Cleavage of basement membrane proteins and sensitivity to metalloprotease inhibitors. Biochemistry Journal 378(1), 383-389 (2004).
[4]. Lee, M.D., She, Y., Soskis, M.J., et al. Human mitochondrial peptide deformylase, a new anticancer target of actinonin-based antibiotics. Journal of Clinical Investigation 114(8), 1107-1116 (2004).