scholarly journals Biochemical and structural characterisation of the second oxidative crosslinking step during the biosynthesis of the glycopeptide antibiotic A47934

2016 ◽  
Vol 12 ◽  
pp. 2849-2864 ◽  
Author(s):  
Veronika Ulrich ◽  
Clara Brieke ◽  
Max J Cryle
Keyword(s):  
Crystal Structure ◽  
Amino Acid Residues ◽  
Glycopeptide Antibiotics ◽  
In Vitro Activity ◽  
Glycopeptide Antibiotic ◽  
Protein Carrier ◽  
Structural Characterisation ◽  
Chemical Complexity ◽  
Peptide Synthetase

The chemical complexity and biological activity of the glycopeptide antibiotics (GPAs) stems from their unique crosslinked structure, which is generated by the actions of cytochrome P450 (Oxy) enzymes that affect the crosslinking of aromatic side chains of amino acid residues contained within the GPA heptapeptide precursor. Given the crucial role peptide cyclisation plays in GPA activity, the characterisation of this process is of great importance in understanding the biosynthesis of these important antibiotics. Here, we report the cyclisation activity and crystal structure of StaF, the D-O-E ring forming Oxy enzyme from A47934 biosynthesis. Our results show that the specificity of StaF is reduced when compared to Oxy enzymes catalysing C-O-D ring formation and that this activity relies on interactions with the non-ribosomal peptide synthetase via the X-domain. Despite the interaction of StaF with the A47934 X-domain being weaker than for the preceding Oxy enzyme StaH, StaF retains higher levels of in vitro activity: we postulate that this is due to the ability of the StaF/X-domain complex to allow substrate reorganisation after initial complex formation has occurred. These results highlight the importance of testing different peptide/protein carrier constructs for in vitro GPA cyclisation assays and show that different Oxy homologues can display significantly different catalytic propensities despite their overall similarities.

Synthesis, characterization, crystal structure and antiproliferative in vitro activity of long-chain aliphatic thiosemicarbazones and their Ni(II) complexes

Polyhedron ◽  
2007 ◽  
Vol 26 (17) ◽  
pp. 5150-5161 ◽  
Author(s):  
Marisa Belicchi-Ferrari ◽  
Franco Bisceglie ◽  
Giorgio Pelosi ◽  
Silvana Pinelli ◽  
Pieralberto Tarasconi
Keyword(s):  
Crystal Structure ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Long Chain

scholarly journals Subinhibitory Dalbavancin Attenuates Exotoxin Production from Methicillin-Sensitive and Methicillin-Resistant Staphylococcus aureusIn Vitro

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Sarah E. Hobdey ◽  
Eva J. Katahira ◽  
Pamela Dockstader ◽  
Stephen M. Davidson ◽  
Laura Bond ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Toxin Production ◽  
Glycopeptide Antibiotics ◽  
Glycopeptide Antibiotic ◽  
Beta Lactam ◽  
Methicillin Resistant ◽  
Content Type ◽  
Recent Success ◽  
Subinhibitory Concentrations

ABSTRACT This study investigated the effects of subinhibitory doses of the lipoglycopeptide antibiotic dalbavancin on Staphylococcus aureus toxin production in vitro. S. aureus toxin production levels were compared to those seen with the natural glycopeptide antibiotic vancomycin and with representative beta-lactam and oxazolidinone antibiotics. While neither dalbavancin nor vancomycin adversely affected toxin production, of these glycopeptide antibiotics, only dalbavancin significantly attenuated toxin production at subinhibitory concentrations. These findings support the recent success of dalbavancin for treatment of staphylococcal infections.

scholarly journals In vitro activity of SK&F 104662, a new glycopeptide antibiotic.

1989 ◽  
Vol 33 (6) ◽  
pp. 965-967 ◽  
Author(s):  
J D Yao ◽  
G M Eliopoulos ◽  
R C Moellering
Keyword(s):  
Vitro Activity ◽  
In Vitro Activity ◽  
Glycopeptide Antibiotic

scholarly journals In Vitro Susceptibilities of Aerobic and Facultative Non-Spore-Forming Gram-Positive Bacilli to HMR 3647 (RU 66647) and 14 Other Antimicrobials

1998 ◽  
Vol 42 (5) ◽  
pp. 1028-1033 ◽  
Author(s):  
Francisco Soriano ◽  
Ricardo Fernández-Roblas ◽  
Raquel Calvo ◽  
Gloria García-Calvo
Keyword(s):  
Vitro Activity ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Glycopeptide Antibiotics ◽  
Erysipelothrix Rhusiopathiae ◽  
In Vitro Activity ◽  
Gram Positive ◽  
Corynebacterium Striatum ◽  
Corynebacterium Pseudodiphtheriticum

ABSTRACT The comparative in vitro activity of the ketolide HMR 3647 (RU 66647) and those of structurally related macrolide-lincosamide-streptogramin compounds (erythromycin, roxithromycin, azithromycin, clarithromycin, josamycin, lincomycin, pristinamycin, and quinupristin-dalfopristin) as well as those of benzylpenicillin, doxycycline, vancomycin, teicoplanin, levofloxacin, and rifapentine against 247 aerobic and facultative non-spore-forming gram-positive bacilli were determined by an agar dilution method. The ketolide was active against most organisms tested exceptCorynebacterium striatum, coryneform CDC group I2, andOerskovia spp. The frequency of resistance to erythromycin and other macrolides as well as that to lincomycin was high. Pristinamycin and, to a lesser extent, quinupristin-dalfopristin were very active, but resistance to these agents was present in some strains of Rhodococcus equi, Listeria spp., C. striatum, Erysipelothrix rhusiopathiae, andOerskovia spp. HMR 3647 was very active against all erythromycin-sensitive and many erythromycin-nonsusceptible strains, especially Corynebacterium minutissimum,Corynebacterium pseudodiphtheriticum, Corynebacterium amycolatum, and Corynebacterium jeikeium. In vitro resistance to benzylpenicillin was common, but doxycycline, vancomycin, and teicoplanin were very active against most organisms tested exceptE. rhusiopathiae, against which glycopeptide antibiotics were not active. The in vitro activity of levofloxacin was remarkable, but resistance to this agent was common for C. amycolatum,Corynebacterium urealyticum, C. jeikeium, andOerskovia spp. strains. Rifapentine was also very active in vitro against many organisms, but resistance to this agent was always present in E. rhusiopathiae and was very common in C. striatum and C. urealyticum.

scholarly journals Pentaminomycins C–E: Cyclic Pentapeptides as Autophagy Inducers from a Mealworm Beetle Gut Bacterium

2020 ◽  
Vol 8 (9) ◽  
pp. 1390 ◽  
Author(s):  
Sunghoon Hwang ◽  
Ly Thi Huong Luu Le ◽  
Shin-Il Jo ◽  
Jongheon Shin ◽  
Min Jae Lee ◽  
...  
Keyword(s):  
Amino Acid ◽  
2D Nmr ◽  
Biosynthetic Gene Cluster ◽  
Amino Acid Residues ◽  
Structural Variations ◽  
Nonribosomal Peptide ◽  
Peptide Synthetase ◽  
Nrps Module ◽  
Mealworm Beetle

Pentaminomycins C–E (1–3) were isolated from the culture of the Streptomyces sp. GG23 strain from the guts of the mealworm beetle, Tenebrio molitor. The structures of the pentaminomycins were determined to be cyclic pentapeptides containing a modified amino acid, N5-hydroxyarginine, based on 1D and 2D NMR and mass spectroscopic analyses. The absolute configurations of the amino acid residues were assigned using Marfey’s method and bioinformatics analysis of their nonribosomal peptide biosynthetic gene cluster (BGC). Detailed analysis of the BGC enabled us to propose that the structural variations in 1–3 originate from the low specificity of the adenylation domain in the nonribosomal peptide synthetase (NRPS) module 1, and indicate that macrocyclization can be catalyzed noncanonically by penicillin binding protein (PBP)-type TE. Furthermore, pentaminomycins C and D (1 and 2) showed significant autophagy-inducing activities and were cytoprotective against oxidative stress in vitro.

Sign in / Sign up

Export Citation Format

Share Document