Berninamycin A

Berninamycin A is a macrocyclic thiopeptide antibiotic first isolated from S. bernensis [1]. Thiopeptides are sulfur containing highly modified macrocyclic antibiotics with a central pyridine/tetrapyridine/dehydropiperidine ring with up to three thiazole substituents on positions 2, 3 and 6. Thiazole antibiotics thiostrepton behaves as proteasome inhibitor in mammalian tumor cells. Berninamycin showed no proteasome inhibitory activity [2]. It has been reported that the action mode of berninamycin on bacterial protein synthesis was related to that of a dissimilar compound thiostrepton. The antibiotics could bind to the complex of 23S RNA with protein L11 and both affect multiple functions of the ribosomal A site [3]. Berninamycin A was involved in inducing the transcriptional activator TipA in Streptomyces [4].

References:
[1] Lau R C M, Rinehart K L.  Berninamycins B, C, and D, minor metabolites from Streptomyces bernensis[J]. The Journal of antibiotics, 1994, 47(12): 1466-1472.
[2] Pandit B, Bhat U G, Gartel A L.  Proteasome inhibitory activity of thiazole antibiotics[J]. Cancer biology & therapy, 2011, 11(1): 43-47.
[3] J.  Thompson, E. Cundliffe and M. J. R. Stark. The mode of action of berninamycin and mechanism of resistance in the producing organism, Streptomyces bernensis. J.Gen.Microbiol. 128(4), 875-884 (1982).
[4].  M. L. Chiu, M. Folcher, T. Katoh, et al. Broad spectrum thiopeptide recognition specificity of the Streptomyces lividans TipAL protein and its role in regulating gene expression. The Journal of Biological Chemisty 274(29), 20578-20586 (1999).