Cationic antimicrobial peptides,
produced by nonribosomal peptide
synthetases (NRPSs), have received great attention in different applications,
including as biocontrol and antimicrobial agents against foodborne
pathogenic bacteria. Also, Brevibacillus spp. is
a competent microorganism to produce cationic antimicrobial peptides
yet has received little attention. Herein, Brevibacillus
laterosporus S62-9 genome mining revealed an integrated
cationic antimicrobial peptide synthetase system that synthesized
brevilaterin. Combining biochemical analysis with bioinformatics elucidated
that the A domain from this system was the MbtH-independent enzyme
and showed activity against the same amino acid in the structure of
brevilaterin. Moreover, the creations of the first three and position
12 residues in the sequence were targeted to bre261, bre270, bre2691A,
and bre2662, respectively. Further analysis of the specificity-conferring
code of the A domain suggested that a tiny difference would make the
activity of the A domain very diverse and the range of substrate selection
would be enlarged or narrowed by changing some residues in the code.
The dissection of this biosynthesis mechanism would contribute to
the successful realization of reasonable artificial design and the
modification of bioactive peptides, and this capable organism also
would be more fully utilized.