29 research outputs found
Recommended from our members
Non-Proteinogenic Amino Acids in Lacticin 481 Analogues Result in More Potent Inhibition of Peptidoglycan Transglycosylation
Lantibiotics are ribosomally synthesized and post-translationally modified peptide natural products that contain the thioether structures lanthionine and methyllanthionine and exert potent antimicrobial activity against Gram-positive bacteria. At present, detailed modes-of-action are only known for a small subset of family members. Lacticin 481, a tricyclic lantibiotic, contains a lipid II binding motif present in related compounds such as mersacidin and nukacin ISK-1. Here, we show that lacticin 481 inhibits PBP1b-catalyzed peptidoglycan formation. Furthermore, we show that changes in potency of analogues of lacticin 481 containing non-proteinogenic amino acids correlate positively with the potency of inhibition of the transglycosylase activity of PBP1b. Thus, lipid II is the likely target of lacticin 481, and use of non-proteinogenic amino acids resulted in stronger inhibition of the target. Additionally, we demonstrate that lacticin 481 does not form pores in the membranes of susceptible bacteria, a common mode-of-action of other lantibiotics.Chemistry and Chemical Biolog
Investigation of the Role of Arg301 Identified in the X-ray Structure of Phosphite Dehydrogenase
Recommended from our members
Minimum Information about a Biosynthetic Gene cluster
A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.Chemistry and Chemical Biolog
Structure–Activity Relationships of the S‑Linked Glycocin Sublancin
Sublancin
is a 37-amino acid antimicrobial peptide belonging to
the glycocin family of natural products. It contains two helices that
are held together by two disulfide bonds as well as an unusual S-glucosidic
linkage to a Cys in a loop connecting the helices. We report the reconstitution
of the biosynthetic pathway to this natural product in <i>Escherichia
coli</i>. This technology enabled the evaluation of the structure–activity
relationships of the solvent-exposed residues in the helices. The
biosynthetic machinery proved tolerant of changes in both helices,
and the bioactivity studies of the resulting mutants show that two
residues in helix B are important for bioactivity, Asn31 and Arg33
NMR Structure of the S‑Linked Glycopeptide Sublancin 168
Sublancin
168 is a member of a small group of glycosylated antimicrobial peptides
known as glycocins. The solution structure of sublancin 168, a 37-amino-acid
peptide produced by <i>Bacillus subtilis</i> 168, has been
solved by nuclear magnetic resonance (NMR) spectroscopy. Sublancin
comprises two α-helices and a well-defined interhelical loop.
The two helices span residues 6–16 and 26–35, and the
loop region encompasses residues 17–25. The 9-amino-acid loop
region contains a β-S-linked glucose moiety attached to Cys22.
Hydrophobic interactions as well as hydrogen bonding are responsible
for the well-structured loop region. The three-dimensional structure
provides an explanation for the previously reported extraordinary
high stability of sublancin 168
The Glycosyltransferase Involved in Thurandacin Biosynthesis Catalyzes Both O- and S‑Glycosylation
The
S-glycosyltransferase SunS is a recently discovered enzyme
that selectively catalyzes the conjugation of carbohydrates to the
cysteine thiol of proteins. This study reports the discovery of a
second S-glycosyltransferase, ThuS, and shows that ThuS catalyzes
both S-glycosylation of the thiol of cysteine and O-glycosylation
of the hydroxyl group of serine in peptide substrates. ThuS-catalyzed
S-glycosylation is more efficient than O-glycosylation, and the enzyme
demonstrates high tolerance with respect to both nucleotide sugars
and peptide substrates. The biosynthesis of the putative products
of the <i>thuS</i> gene cluster was reconstituted <i>in vitro</i>, and the resulting S-glycosylated peptides thurandacin
A and B exhibit highly selective antimicrobial activity toward <i>Bacillus thuringiensis.</i