Roseocin, a novel two-component lantibiotic from an actinomycete.
Mangal SinghSandeep ChaudharyDipti SareenPublished in: Molecular microbiology (2019)
Lantibiotics are lanthionine ring containing natural products that belong to the class of ribosomally synthesized and posttranslationally modified peptides (RiPPs). Recent expansion in the availability of microbial genome data and in silico analysis tools have accelerated the discovery of these promising alternatives to antibiotics. Following the genome-mining approach, a biosynthetic gene cluster for a putative two-component lantibiotic, roseocin, was identified in the genome of an Actinomycete, Streptomyces roseosporus NRRL 11379. Posttranslationally modified lanthipeptides of this cluster were obtained by heterologous expression of the genes in Escherichia coli, and were in vitro reconstituted to their bioactive form by exploiting commercial proteases like endoproteinase GluC, and proteinase K. The two peptides displayed synergistic antimicrobial activity against Gram-positive bacteria including the WHO high-priority pathogens, MRSA and VRE. Structural characterization confirmed the installation of four (methyl)lanthionine rings with an indispensable disulfide bond in the α-peptide, and six (methyl)lanthionine rings in the β-peptide, by a single promiscuous lanthionine synthetase, RosM. Roseocin is the first two-component lantibiotic from a non-Firmicute, with extensive lanthionine bridging.
Keyphrases
- genome wide
- escherichia coli
- gram negative
- dna methylation
- staphylococcus aureus
- small molecule
- copy number
- methicillin resistant staphylococcus aureus
- genome wide identification
- high throughput
- molecular docking
- microbial community
- amino acid
- electronic health record
- multidrug resistant
- gene expression
- cancer therapy
- binding protein
- drug delivery
- big data
- data analysis
- transcription factor
- high density
- klebsiella pneumoniae
- saccharomyces cerevisiae
- bioinformatics analysis