Inhibition of Protein Synthesis by Bottromycin A2 and Its Hydrazide

Mechanism of Action of Ribosomally Synthesized and Post-Translationally Modified Peptides

“…Although bottromycins are known protein synthesis inhibitors, their target was difficult to resolve. Isotopic labeling studies showed that bottromycin A2 inhibits protein synthesis in vitro and in vivo . Inhibition was dependent on base composition as significant translational stalling was observed for poly-C but not poly-U or poly-A.…”

“… Bottromycins contain a class-defining macrolactamidine and a suite of other modifications, including a decarboxylated C-terminal thiazole as well as several C - and O -methylations on the side chains (Figure ). Studies on the MOA of the bottromycins were carried out primarily by studying bottromycin A2 ( 71 ), which was among the first two isolated members of this class and the subject of the total synthetic effort. , The antibacterial activity of bottromycin has been demonstrated for Mycoplasma, MRSA, VRE, and the rice plant pathogen Xanthomonas oryzae pv oryzae with MIC values in the low μM range. ,, …”

Antibiotic inhibitors of the bacterial ribosome.

“…The inhibitory effects of bottromycin on intact cells and extracts from E. coli were studied by Tanaka et al (197). They observed an inhibition of the transfer of aminoacyl tRNA into protein without concomitant inhibition of amino acid attachment to tRNA.…”

Translation-Targeting RiPPs and Where to Find Them

“…Bottromycins are extensively modified RiPPs that exhibit potent antimicrobial activity against the drug-resistant human pathogens including vancomycin-resistant Enterococcus (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) (Shimamura et al, 2009). In early works, bottromycin A2 was demonstrated to inhibit protein synthesis both in vitro and in vivo (Tanaka et al, 1966). Further studies showed that the action of bottromycin does not interfere with the peptide bond formation and translocation steps.…”