Structural Organization of Brevilaterin Biosynthesis in Brevibacillus laterosporus S62-9: A Novel MbtH-Independent Cationic Antimicrobial Peptide Synthetase System.

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.