Re-evaluation of in vitro activity of primycin against prevalent multiresistant bacteria

Feiszt, Péter; Mestyan, G; Kerényi, Mónika; Dobay, Orsolya; Szabó, Judit; Dombrádi, Zsuzsanna; Urbán, Edit; Emödy, Levente

doi:10.1016/j.ijmm.2014.08.001

Cited by 12 publications

(17 citation statements)

References 20 publications

(7 reference statements)

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“…These clusters also contain genes encoding homologues of SamR0482. One of these genes clusters has recently been reported to direct the biosynthesis of the primycin complex of antibiotics24, which has been used in the clinic as a topical antibiotic and has recently been shown to be effective against multi-drug resistant Gram-positive pathogens, including methicillin- and mupirocin-resistant Staphylococcus aureus 25. Butylmalonyl-CoA is incorporated into primycin A1 ( 41 ) (Fig.…”

Section: Resultsmentioning

confidence: 99%

A crotonyl-CoA reductase-carboxylase independent pathway for assembly of unusual alkylmalonyl-CoA polyketide synthase extender units

et al. 2016

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Type I modular polyketide synthases assemble diverse bioactive natural products. Such multienzymes typically use malonyl and methylmalonyl-CoA building blocks for polyketide chain assembly. However, in several cases more exotic alkylmalonyl-CoA extender units are also known to be incorporated. In all examples studied to date, such unusual extender units are biosynthesized via reductive carboxylation of a, b-unsaturated thioesters catalysed by crotonyl-CoA reductase/carboxylase (CCRC) homologues. Here we show using a chemicallysynthesized deuterium-labelled mechanistic probe, and heterologous gene expression experiments that the unusual alkylmalonyl-CoA extender units incorporated into the stambomycin family of polyketide antibiotics are assembled by direct carboxylation of medium chain acyl-CoA thioesters. X-ray crystal structures of the unusual b-subunit of the acyl-CoA carboxylase (YCC) responsible for this reaction, alone and in complex with hexanoyl-CoA, reveal the molecular basis for substrate recognition, inspiring the development of methodology for polyketide bio-orthogonal tagging via incorporation of 6-azidohexanoic acid and 8-nonynoic acid into novel stambomycin analogues.

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Section: Resultsmentioning

confidence: 99%

A crotonyl-CoA reductase-carboxylase independent pathway for assembly of unusual alkylmalonyl-CoA polyketide synthase extender units

et al. 2016

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“…The overexpression of FA synthesis related genes in low-producer S. azurea DSM 44631 strain suggests that biosynthetic activity of FA and polyketide related machinery is not a clear sequential process, rather should be considered an overlapping even at least partially. Primycin, a non-polyene marginolactone antibiotic produced by filamentous bacteria S. azurea, possesses high antimicrobial activity against frequent G+ pathogens, including clinically prevalent multidrug-resistant strains (Feiszt et al 2014). To protect themselves against their own bioactive metabolites, self-resistance mechanism for antibiotic producers are crucial.…”

Section: Discussionmentioning

confidence: 99%

Structural and functional comparison of Saccharomonospora azurea strains in terms of primycin producing ability

Kovacs

Seffer

Pénzes-Hűvös

et al. 2020

World J Microbiol Biotechnol

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Emerging and re-emerging microbial pathogens, together with their rapid evolution and adaptation against antibiotics, highlight the importance not only of screening for new antimicrobial agents, but also for deepening knowledge about existing antibiotics. Primycin is a large 36-membered non-polyene macrolide lactone exclusively produced by Saccharomonospora azurea. This study provides information about strain dependent primycin production ability in conjunction with the structural, functional and comparative genomic examinations. Comparison of high- and low-primycin producer strains, transcriptomic analysis identified a total of 686 differentially expressed genes (DEGs), classified into diverse Cluster of Orthologous Groups. Among them, genes related to fatty acid synthesis, self-resistance, regulation of secondary metabolism and agmatinase encoding gene responsible for catalyze conversion between guanidino/amino forms of primycin were discussed. Based on in silico data mining methods, we were able to identify DEGs whose altered expression provide a good starting point for the optimization of fermentation processes, in order to perform targeted strain improvement and rational drug design.

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“…[31][32][33] Later in 1998, it was found that rustamicin (18) and its congeners mediate their fungicidal activity via inhibition of the fungal inositol phosphoceramide synthase resulting in interrupted sphingolipid biosynthesis. 34 In 1980, further eighteen compounds called mycinamicin I-XVIII (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43) were added to the 16-membered macrolide antibiotics family from a soil derived-M. griseorubida strain. Interestingly, mycinamicins showed potent bacteriostatic activity against Gram-positive pathogenic bacteria (MIC 0.1-3.12 mg mL À1 ).…”

Section: Macrolidesmentioning

confidence: 99%

“…42 In 2014, this interesting antibiotic was re-evaluated against prevalent multi-resistant Gram-positive bacteria responsible for common skin infections. 43 Besides its promising antibiotic activities, perimycin (45) possesses signicant antifungal effects against a wide range of pathogenic fungi. 44 Its complex formation with the fungal cell membrane ergosterol is considered the primary mode of action responsible for its antifungal properties.…”

Section: Macrolidesmentioning

confidence: 99%

The genus Micromonospora as a model microorganism for bioactive natural product discovery

et al. 2020

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Re-evaluation of in vitro activity of primycin against prevalent multiresistant bacteria

Cited by 12 publications

References 20 publications

A crotonyl-CoA reductase-carboxylase independent pathway for assembly of unusual alkylmalonyl-CoA polyketide synthase extender units

A crotonyl-CoA reductase-carboxylase independent pathway for assembly of unusual alkylmalonyl-CoA polyketide synthase extender units

Structural and functional comparison of Saccharomonospora azurea strains in terms of primycin producing ability

The genus Micromonospora as a model microorganism for bioactive natural product discovery

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