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J Biol Chem, Vol. 273, Issue 36, 23134-23142, September 4, 1998
From the Department of Chemistry and Biochemistry, University of
Maryland, College Park, Maryland 20742
An antimicrobial peptide produced by
Bacillus subtilis 168 was isolated and characterized. It
was named sublancin 168, and its behavior during Edman sequence
analysis and its NMR spectrum suggested that sublancin is a
dehydroalanine-containing lantibiotic. A hybridization probe based on
the peptide sequence was used to clone the presublancin gene, which
encoded a 56-residue polypeptide consisting of a 19-residue leader
segment and a 37-residue mature segment. The mature segment contained
one serine, one threonine, and five cysteine residues. Alkylation of
mature sublancin showed no free sulfhydryl groups, suggesting that one
sulfydryl had formed a
Identification and Characterization of the Structural and
Transporter Genes for, and the Chemical and Biological Properties
of, Sublancin 168, a Novel Lantibiotic Produced by Bacillus
subtilis 168
-methyllanthionine bridge with a
dehydrobutyrine derived by posttranslational modification of threonine;
with the other four cysteines forming two disulfide bridges. It is
unprecedented for a lantibiotic to contain a disulfide bridge. The
sublancin leader was similar to known type AII lantibiotics, containing
a double-glycine motif that is typically recognized by dual-function
transporters. A protein encoded immediately downstream from the
sublancin gene possessed features of a dual-function ABC transporter
with a proteolytic domain and an ATP-binding domain. The antimicrobial
activity spectrum of sublancin was like other lantibiotics, inhibiting
Gram-positive bacteria but not Gram-negative bacteria; and like the
lantibiotics nisin and subtilin in its ability to inhibit both
bacterial spore outgrowth and vegetative growth. Sublancin is an
extraordinarily stable lantibiotic, showing no degradation or
inactivation after being stored in aqueous solution at room temperature
for 2 years. The fact that sublancin is a natural product of B. subtilis 168, for which a great deal of genetic information is
available, including the entire sequence of its genome, suggests that
sublancin will be an especially good model for studying the potential
of lantibiotics as sources of novel biomaterials.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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