title: Pseudomycoicidin, a Class II Lantibiotic from Bacillus pseudomycoides.
abstract: Lantibiotics are ribosomally synthesized antimicrobial peptides with substantial posttranslational modifications. They are characterized by the unique amino acids lanthionine and methyllanthionine, which are introduced by dehydration of Ser/Thr residues and linkage of the resulting dehydrated amino acids with Cys residues. BLAST searches using the mersacidin biosynthetic enzyme (MrsM) in the NCBI database revealed a new class II lantibiotic gene cluster in Bacillus pseudomycoides DSM 12442. Production of an antimicrobial substance with activity against Gram-positive bacteria was detectable in a cell wash extract of this strain. The substance was partially purified, and mass spectrometric analysis predicted a peptide of 2,786 Da in the active fraction. In order to characterize the putative lantibiotic further, heterologous expression of the predicted biosynthetic genes was performed in Escherichia coli. Coexpression of the prepeptide (PseA) along with the corresponding modification enzyme (PseM) resulted in the production of a modified peptide with the corresponding mass, carrying four out of eight possible dehydrations and supporting the presence of four thioether and one disulfide bridge. After the proteolytic removal of the leader, the core peptide exhibited antimicrobial activity. In conclusion, pseudomycoicidin is a novel lantibiotic with antimicrobial activity that was heterologously produced in E. coli.
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University of Bonn, Bonn, Germany.
authors.forename: Shradha
authors.initials: S
authors.lastname: Basi-Chipalu
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University of Bonn, Bonn, Germany.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Dischinger
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University of Bonn, Bonn, Germany.
authors.forename: Michaele
authors.initials: M
authors.lastname: Josten
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University of Bonn, Bonn, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Szekat
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University of Bonn, Bonn, Germany.
authors.forename: Annegret
authors.initials: A
authors.lastname: Zweynert
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University of Bonn, Bonn, Germany.
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Sahl
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University of Bonn, Bonn, Germany bierbaum@mibi03.meb.uni-bonn.de.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Bierbaum
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001407:Bacillus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001430:Bacteriocins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008969:Molecular Sequence Data; D016415:Sequence Alignment
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001430:Bacteriocins