Thiol-disulfide oxidoreductases are essential for the production of the lantibiotic sublancin 168.
Thiol-disulfide oxidoreductases are required for disulfide bond formation in proteins that are exported from the cytoplasm. Four enzymes of this type, termed BdbA, BdbB, BdbC, and BdbD, have been identified in the Gram-positive eubacterium Bacillus subtilis. BdbC and BdbD have been shown to be critical for the folding of a protein required for DNA uptake during natural competence. In contrast, no function has been assigned so far to the BdbA and BdbB proteins. The bdbA and bdbB genes are located in one operon that also contains the genes specifying the lantibiotic sublancin 168 and the ATP-binding cassette transporter SunT. Interestingly sublancin 168 contains two disulfide bonds. The present studies demonstrate that SunT and BdbB, but not BdbA, are required for the production of active sublancin 168. In addition, the BdbB paralogue BdbC is at least partly able to replace BdbB in sublancin 168 production. These observations show the unprecedented involvement of thiol-disulfide oxidoreductases in the synthesis of a peptide antibiotic. Notably BdbB cannot complement BdbC in competence development, showing that these two closely related thiol-disulfide oxidoreductases have different, but partly overlapping, substrate specificities.
Dorenbos
Ronald
R
Department of Pharmaceutical Biology, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, the Netherlands.
Stein
Torsten
T
Kabel
Jorrit
J
Bruand
Claude
C
Bolhuis
Albert
A
Bron
Sierd
S
Quax
Wim J
WJ
Van Dijl
Jan Maarten
JM
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000201:enzymology; D001426:Bacterial Proteins; D001430:Bacteriocins; D001483:Base Sequence; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000201:enzymology; D004247:DNA / Q000378:metabolism; D004220:Disulfides; D006020:Glycopeptides; D008969:Molecular Sequence Data; D010455:Peptides; D010957:Plasmids / Q000378:metabolism; D011490:Protein Disulfide Reductase (Glutathione) / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013379:Substrate Specificity
D018528:ATP-Binding Cassette Transporters; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001430:Bacteriocins; D004220:Disulfides; D006020:Glycopeptides; C445678:LcnC protein, bacteria; D010455:Peptides; C114602:sublancin 168; D004247:DNA; D011490:Protein Disulfide Reductase (Glutathione)