Chlorinated Glycopeptide Antibiotic Peptide Precursors Improve Cytochrome P450-Catalyzed Cyclization Cascade Efficiency

Biochemistry ◽  
2017 ◽  
Vol 56 (9) ◽  
pp. 1239-1247 ◽  
Author(s):  
Madeleine Peschke ◽  
Clara Brieke ◽  
Rob J. A. Goode ◽  
Ralf B. Schittenhelm ◽  
Max J. Cryle
Keyword(s):  
Cytochrome P450 ◽  
Glycopeptide Antibiotic ◽  
Peptide Precursors ◽  
Antibiotic Peptide

More than just recruitment: the X-domain influences catalysis of the first phenolic coupling reaction in A47934 biosynthesis by Cytochrome P450 StaH

2016 ◽  
Vol 12 (10) ◽  
pp. 2992-3004 ◽  
Author(s):  
Veronika Ulrich ◽  
Madeleine Peschke ◽  
Clara Brieke ◽  
Max J. Cryle
Keyword(s):  
Cytochrome P450 ◽  
Coupling Reaction ◽  
Glycopeptide Antibiotic

Cytochrome P450 StaH catalyses the first cyclisation reaction in the biosynthesis of the glycopeptide antibiotic A47934 via recruitment to the NRPS machinery through interaction with the X-domain.

scholarly journals Inhibition of peptidoglycan biosynthesis in vancomycin-susceptible and -resistant bacteria by a semisynthetic glycopeptide antibiotic.

1996 ◽  
Vol 40 (10) ◽  
pp. 2356-2362 ◽  
Author(s):  
N E Allen ◽  
J N Hobbs ◽  
T I Nicas
Keyword(s):  
Late Stage ◽  
Substrate Inhibition ◽  
Resistant Bacteria ◽  
Cross Linking ◽  
Glycopeptide Antibiotic ◽  
Peptidoglycan Biosynthesis ◽  
Aerococcus Viridans ◽  
Muramyl Peptide ◽  
Peptide Precursors ◽  
Vancomycin Resistant

LY191145 is a p-chlorobenzyl derivative of LY264826 (A82846B) with activity against both vancomycin-susceptible and -resistant enterococci. Incorporation of L-[14C]lysine into peptidoglycan of intact vancomycin-susceptible and -resistant Enterococcus faecium was inhibited by LY191145 (50% inhibitory concentrations of 1 and 5 microgram/ml, respectively). Inhibition was accompanied by accumulation of UDP-muramyl-peptide precursors in the cytoplasm. This agent inhibited late-stage steps in peptidoglycan biosynthesis in permeabilized E. faecium when either the UDP-muramyl-pentapeptide precursor from vancomycin-susceptible E. faecium or the UDP-muramyl-pentadepsipeptide precursor from vancomycin-resistant E. faecium was used as a substrate. Inhibition of late-stage steps led to accumulation of an N-acetyl-[14C]glucosamine-labeled lipid intermediate indicative of inhibition of the transglycosylation step. Inhibition of peptidoglycan polymerization without affecting cross-linking in a particulate membrane-plus-wall-fragment assay from Aerococcus viridans was consistent with this explanation. The fact that inhibition of peptidoglycan biosynthesis by LY191145 was not readily antagonized by an excess of free acyl-D-alanyl-D-alanine or acyl-D-alanyl-D-lactate ligands indicates that the manner in which this compound inhibits transglycosylation may not be identical to that of vancomycin.

Rapid access to glycopeptide antibiotic precursor peptides coupled with cytochrome P450-mediated catalysis: towards a biomimetic synthesis of glycopeptide antibiotics

2015 ◽  
Vol 13 (7) ◽  
pp. 2012-2021 ◽  
Author(s):  
Clara Brieke ◽  
Veronika Kratzig ◽  
Kristina Haslinger ◽  
Andreas Winkler ◽  
Max J. Cryle
Keyword(s):  
Cytochrome P450 ◽  
Biomimetic Synthesis ◽  
Carrier Protein ◽  
Cytochrome P450 Enzyme ◽  
Glycopeptide Antibiotics ◽  
Glycopeptide Antibiotic ◽  
Rapid Access ◽  
P450 Enzyme ◽  
Mediated Catalysis

One Cytochrome P450 enzyme performs the phenolic crosslinking of a range of chemically synthesized, carrier-protein loaded glycopeptide antibiotic precursor peptides.

scholarly journals Chemotactic and protease-inhibiting activities of antibiotic peptide precursors

FEBS Letters ◽  
1993 ◽  
Vol 317 (3) ◽  
pp. 255-258 ◽  
Author(s):  
Donatella Verbanac ◽  
Margherita Zanetti ◽  
Domenico Romeo
Keyword(s):  
Peptide Precursors ◽  
Antibiotic Peptide
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