Structure-activity studies of irumamycin type macrolides from Streptomyces sp. INA-Ac-5812

Alferova, Vera A.; Shuvalov, Maxim V.; Новиков, Роман А.; Тренин, А. С.; Dezhenkova, Lubov G.; Gladkikh, Elena G.; Lapchinskaya, Olda A.; Kulyaeva, V. V.; Bychkova, Olga P.; Mirchink, Elena P.; Solyev, Pavel N.; Kudryakova, Gulnara; Korshun, Vladimir A.; Tyurin, Anton P.

doi:10.1016/j.tetlet.2019.04.051

Cited by 8 publications

(12 citation statements)

References 24 publications

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“…S. roseoflavus INA strains are being widely studied to investigate a number of biologically active components with antimicrobial functions including the macrolide-type antibiotic irumamycin, which is active against opportunistic yeasts and fungi ( Shashkov et al, 2011 ; Lapchinskaya et al, 2015 ). Previously, two structural homologs (isoirumamycin and the compound X-1495B) identified from INA-Ac-5812 strains and structurally characterized by NMR spectroscopy were found to have previously unknown stereo-configuration ( Alferova et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

A Novel Peptide Antibiotic Produced by Streptomyces roseoflavus Strain INA-Ac-5812 With Directed Activity Against Gram-Positive Bacteria

et al. 2020

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In this work, we report the isolation and detailed functional characterization for the new non-ribosomally synthesized antibiotic 5812-A/C, which was derived from metabolites of Streptomyces roseoflavus INA-Ac-5812. According to its chemical structure, the studied 5812-A/C preliminary is composed of a cyclic peptide part covalently bounded with an arabinose residue. N-terminal amino acid sequencing of the native peptide has identified its partial structure of Leu-Asp-Gly-Ser-Gly and consisting of a Tyr residue that is supposed to have a two-component peptide nature for the molecule studied. However, the structural analysis of the antibiotic complex derived from S. roseoflavus INA-Ac-5812 is still ongoing. The mechanism of action of 5812-A/C was assessed in comparison with its most related analog, the lipopeptide antibiotic daptomycin, given the presence in both antimicrobials of an L-kynurenine amino acid residue. The inhibitory activity of 5812-A/C against Gram-positive bacteria including methicillin-resistant strain of Staphylococcus aureus was similar to daptomycin. The mechanism of action of 5812-A/C was associated with the disruption of membrane integrity, which differs in comparison with daptomycin and is most similar to the antimicrobial membranedisturbing peptides. However, 5812-A/C demonstrated a calcium-dependent mode of action. In addition, unlike daptomycin, 5812-A/C was able to penetrate mature biofilms and inhibit the metabolic activity of embedded S. aureus cells. At the same time, 5812-A/C has no hemolytic activity toward erythrocyte, but possessed weak cytotoxic activity represented by heterochromatin condensation in human buccal epithelium cells. The biological properties of the peptide 5812-A/C suggest its classification as a calcium-dependent antibiotic effective against a wide spectrum of Gram-positive pathogenic bacteria.

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Section: Discussionmentioning

confidence: 99%

A Novel Peptide Antibiotic Produced by Streptomyces roseoflavus Strain INA-Ac-5812 With Directed Activity Against Gram-Positive Bacteria

et al. 2020

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“…20 Initially, gausemycins were characterized as intrinsically fluorescent peptides with a broad spectrum of antibiotic activity. Crude extracts were separated from the antifungal fraction containing irumamycin/venturicidin-type polyketide macrolides 22 and purified by solid-phase extraction on LPS-500-H resin followed by reversed-phase chromatography on C18 column yielding gausemycin concentrate. Hydrolysis of the antibiotic concentrate showed that the blue fluorescence of the studied peptides originates entirely from a chlorinated amino acid -4-chloro-L-kynurenine (ClKyn).…”

Section: Resultsmentioning

confidence: 99%

“…Crude extracts were washed with ethyl acetate to separate antifungal fraction (containing irumamycin and related compounds). 22 Resulting mixtures were subjected to sorption on LPS-500-H resin in order to set apart low molecular weight impurities and after that, additional stage preparative reversed-phase C18 HPLC was applied, yielding mixture of gausemycins A and B fraction without hydrophobic impurities. Solid-phase sorption on LPS-500-H. Preparative solid-phase extraction was performed on cartridges, filled with LPS-500-H sorbent.…”

Section: Discussionmentioning

confidence: 99%

Gausemycins A,B: Cyclic Lipoglycopeptides fromStreptomycessp.**

et al. 2021

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We report a novel family of natural lipoglycopeptides produced by Streptomyces sp. INA-Ac-5812. Two major components of the mixture, named gausemycins A and B, were isolated, and their structures were elucidated. The compounds are cyclic peptides with a unique peptide core and several remarkable structural features, including unusual positions of D-amino acids, lack of the Ca 2+ -binding Asp-X-Asp-Gly (DXDG) motif, tyrosine glycosylation with arabinose, presence of 2-amino-4-hydroxy-4-phenylbutyric acid (Ahpb) and chlorinated kynurenine (ClKyn), N-acylation of the ornithine side chain. These major components of the peptide antibiotic family have pronounced activity against Grampositive bacteria. The mechanism of action of gausemycins was explored by a number of methods, showing significant differences compared to glycopeptides and related lipopeptides. Gausemycins exhibit only slight Ca 2+ -dependence of antimicrobial activity and induce no pore formation at low concentrations. Moreover, there is no detectable accumulation of cell wall biosynthesis precursors under treatment with gausemycins.

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“…Gausemycins were obtained as white solids, their structure was elucidated using NMR data (chemical shifts are presented in Table S8). Physico-chemical characteristics of obtained compounds are listed below: Gausemycin A: colorless amorphous powder; [α] 22 D -6.9 (c 0. Deglycosylation of gausemycin A.…”

Section: Methodsmentioning

confidence: 99%

Gausemycins A,B – Cyclic Lipoglycopeptides from Streptomyces Sp.

Tyurin¹,

Alferova²,

Paramonov³

et al. 2021

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We report a novel family of natural lipoglycopeptides produced by Streptomyces sp. INA-Ac-5812. Two major components of the mixture, named gausemycins A and B, were isolated, and their structures were elucidated. The com-pounds are cyclic peptides with a unique peptide core and several remarkable structural features, including unusual posi-tions of D-amino acids, lack of the Ca2+-binding Asp-X-Asp-Gly (DXDG) motif, tyrosine glycosylation with arabinose, presence of 2-amino-4-hydroxy-4-phenylbutyric acid (Ahpb) and chlorinated kynurenine (ClKyn), N-acylation of the or-nithine side chain. These major components of the peptide antibiotic family have pronounced activity against Gram-positive bacteria. The mechanism of action of gausemycins was explored by a number of methods, showing significant differences compared to glycopeptides and related lipopeptides. Gausemycins exhibit only slight Ca2+-dependence of an-timicrobial activity and induce no pore formation at low concentrations. Moreover, there is no detectable accumulation of cell wall biosynthesis precursors under treatment with gausemycins.

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Structure-activity studies of irumamycin type macrolides from Streptomyces sp. INA-Ac-5812

Cited by 8 publications

References 24 publications

A Novel Peptide Antibiotic Produced by Streptomyces roseoflavus Strain INA-Ac-5812 With Directed Activity Against Gram-Positive Bacteria

A Novel Peptide Antibiotic Produced by Streptomyces roseoflavus Strain INA-Ac-5812 With Directed Activity Against Gram-Positive Bacteria

Gausemycins A,B: Cyclic Lipoglycopeptides fromStreptomycessp.**

Gausemycins A,B – Cyclic Lipoglycopeptides from Streptomyces Sp.

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