Rapid Discovery of Glycocins through Pathway Refactoring in Escherichia coli

Hengqian Ren, Subhanip Biswas, Sherri Ho, Wilfred A. Van Der Donk, Huimin Zhao

Research output: Contribution to journalArticle

Abstract

Glycocins (glycosylated bacteriocins) are a family of ribosomally synthesized and post-translationally modified peptides with antimicrobial activities against pathogens of interest, including methicillin-resistant Staphylococcus aureus, representing a promising source of new antibiotics. Glycocins are still largely underexplored, and thus far, only six glycocins are known. Here, we used genome mining to identify 50 putative glycocin biosynthetic gene clusters and then chose six of them with distinct features for further investigation. Through two rounds of plug-and-play pathway refactoring and expression in Escherichia coli BL21(DE3), four systems produced novel glycocins. Further structural characterization revealed that one of them, which belongs to the enterocin 96-type glycocins, was diglucosylated on a single serine. The other three compounds belong to the SunA/ThuA-type glycocins and exhibit a antimicrobial spectrum narrower than that of sublancin, the best characterized member in this group, even though they share a similar disulfide topology and glycosylation. Further evaluation of their bioactivities with free glucose at high concentrations suggested that their antimicrobial mechanisms might be both glycocin- and species-specific. These glycocins with distinct features significantly broaden our knowledge and may lead to the discovery of new classes of antibiotics.

Original languageEnglish (US)
Pages (from-to)2966-2972
Number of pages7
JournalACS chemical biology
Volume13
Issue number10
DOIs
StatePublished - Oct 19 2018

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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