Structural Characterization and Bioactivity Analysis of the Two-Component Lantibiotic Flv System from a Ruminant Bacterium. Issue 2 (18th February 2016)

• Record Type: Journal Article
• Authors: Zhao, Xiling; van der Donk, Wilfred A.
• Is Part Of: Cell chemical biology. Volume 23:Issue 2(2016)
• Page Start: 246
• Page End: 256
• Publication Date: 2016-02-18
• Subjects: Biochemistry -- Periodicals; 572.05
• DOI: 10.1016/j.chembiol.2015.11.014
• Languages: English
• ISSNs: 2451-9456

Abstract

Summary: The discovery of new ribosomally synthesized and post-translationally modified peptide natural products (RiPPs) has greatly benefitted from the influx of genomic information. The lanthipeptides are a subset of this class of compounds. Adopting the genome-mining approach revealed a novel lanthipeptide gene cluster encoded in the genome of Ruminococcus flavefaciens FD-1, an anaerobic bacterium that is an important member of the rumen microbiota of livestock. The post-translationally modified peptides were produced via heterologous expression in Escherichia coli . Subsequent structural characterization and assessment of their bioactivity revealed features reminiscent of and distinct from previously reported lanthipeptides. The lanthipeptides of R. flavefaciens FD-1 represent a unique example within two-component lanthipeptides, consisting of a highly conserved α-peptide and a diverse set of eight β-peptides. Graphical Abstract: Highlights: Production of nine different lanthipeptides from an anaerobic ruminant bacterium Novel example of substrate diversification in two-component lanthipeptides Flavecin synthetase FlvM2 converts eight diverse peptides into polycyclic structures Abstract : An unusual gene cluster from Ruminococcus flavefaciens contains 12 substrate and two lanthipeptide synthetase genes. The post-translationally modified peptides were produced in E. coli and comprise four structurally conserved lipid II binding peptides and eight structurally diverse β-peptides, some of which displayed synergistic antimicrobial activity.