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.