A Combinatorial Yeast Overlay Method for the Isolation of Antibacterial Oligopeptides

• DOI: 10.1007/s40011-013-0257-8
• Publication Date: 2013-11-11T15:09:50Z
• Authors: Ran He; Liang Cui; Yan Cao; Zhixue Wang; Kai Wang; Min Fu; Shaoyun Song; Chuanfu Dong; Xiaoxuan Wu; Ye Gao; Xiaoxiao Zhang; Fan Feng; Xiaoqian Ma; Qiuyun Liu
• Keywords: Oligopeptide; Antibacterial peptide; Isolation

The abuse of antibiotics has led to the emergence of many resistant bacteria, which threaten public health on a global scale. Conventional pipelines for antibiotic discovery are gradually exhausted. Here a combinatorial yeast overlay method is presented for the isolation of antibacterial oligopeptides. Three antibacterial dipeptide and tripeptides were discovered from 20 attempts, two of which possess glycosylation sites. Although the antibacterial effects were modest against several tested bacteria including a multi-resistant Staphylococcus aureus strain Y5, they are amenable to chemical modifications to enhance potency. This cost-effective method can circumvent the expensive chemical peptide synthesis process. The eukaryotic host Saccharomyces cerevisiae adopted for peptide expression could serve as a surrogate biosafety assay system for antibacterial peptides. The small size of the oligopeptides render them attractive candidates for drug development. Given the vast combinatorial diversity of peptides, the reservoir may serve as a rich source of drug leads.