The rising occurrence of multi-drug resistant bacterial infections has projected an exponential increase in mortality if left unabated by antibiotic development. Identification and development of compounds that are unhindered by resistance mechanisms and target alternative binding sites could lead to promising therapeutics. The antimicrobial peptide oncocin is rich in prolines and targets the bacterial ribosome, which leads to arrest of translation. Systematic mutagenesis of oncocin will serve as a model to enhance the antimicrobial properties of the naturally derived antibiotic. Oncocin analogs were encoded onto a plasmid and expressed in Escherichia coli to evaluate the effects of truncations and substitutions on antimicrobial activity. Truncation of the C-terminus by four amino acids and substitutions at positions 4 and 7 with lysine and arginine, respectively, provided an analog that exhibited increased antimicrobial activity over the parent peptide. Minimum inhibitory concentration and molecular dynamic simulations were carried out to support these findings. The in vivo expression system has provided a functional approach to evaluate antibacterial peptides in their target organism for development of peptide antibiotics.

Engineering the antimicrobial peptide oncocin to enhance activity

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