Activation of subtilin precursors by Bacillus subtilis extracellular serine proteases subtilisin (AprE), WprA, and Vpr.
The maturation of the peptide antibiotic (lantibiotic) subtilin in Bacillus subtilis ATCC 6633 includes posttranslational modifications of the propeptide and proteolytic cleavage of the leader peptide. To identify subtilin processing activities, we used antimicrobial inactive subtilin precursors consisting of the leader peptide which was still attached to the fully matured propeptide. Two extracellular B. subtilis proteases were able to activate subtilin precursors, the commercially available serine protease prototype subtilisin (AprE) and WprA. The latter was isolated from B. subtilis WB600, a strain deficient in six extracellular proteases. Surprisingly, the aprE wprA double mutant of the ATCC 6633 strain was still able to produce active subtilin, however, with a reduced production rate. No subtilin processing was found within the culture supernatant of the WB800 strain, which is deficient in eight extracellular proteases. Vpr was identified as the third protease capable to process subtilin.
Corvey
Carsten
C
Institut für Pharmazeutische Chemie, Johann Wolfgang Goethe-Universität, Marie-Curie-Str. 9-11, 60439, Frankfurt/M, Germany.
Stein
Torsten
T
Düsterhus
Stefanie
S
Karas
Michael
M
Entian
Karl-Dieter
KD
D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism* / Q000494:pharmacology; D001412:Bacillus subtilis / Q000201:enzymology* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001430:Bacteriocins; D002473:Cell Wall / Q000201:enzymology; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D010455:Peptides; D011498:Protein Precursors / Q000378:metabolism* / Q000494:pharmacology; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D013381:Subtilisins / Q000737:chemistry / Q000378:metabolism
D023181:Antimicrobial Cationic Peptides; C088074:AprE protein, Bacteria; D001426:Bacterial Proteins; D001430:Bacteriocins; D026901:Membrane Transport Proteins; D010455:Peptides; D011498:Protein Precursors; D012697:Serine Endopeptidases; D013381:Subtilisins; C104015:WprA protein, Bacillus subtilis; C002836:subtilin