Structural and functional comparison of Saccharomonospora azurea strains in terms of primycin producing ability
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ORIGINAL PAPER
Structural and functional comparison of Saccharomonospora azurea strains in terms of primycin producing ability Márk Kovács1,3 · Dénes Seffer1 · Ágota Pénzes‑Hűvös1 · Ákos Juhász2 · Ildikó Kerepesi3 · Kitti Csepregi3 · Andrea Kovács‑Valasek3 · Csaba Fekete3 Received: 16 July 2020 / Accepted: 15 September 2020 / Published online: 29 September 2020 © The Author(s) 2020
Abstract 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. Keywords Polyketide biosynthetic genes · Primycin · Saccharomonospora azurea · Structural and functional genomics
Introduction Actinomycetales are known as natural producers of a wide range of biologically active secondary metabolites that exhibit remarkable clinical importance (Jakubiec-Krzesniak et al. 2018; Solecka et al. 2012). Primycin, produced by a Gram-positive (G+) filamentous bacteria Saccharomonospora azurea, is a 36-membered marginolactone antibiotic that possesses high antimicrobial activity against frequent Gram-positive pathogens, including clinically prevalent Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11274-020-02935-x) contains supplementary material, which is available to authorized users. * Csaba Fekete [email protected] 1
PannonPharma Pharmaceutical Ltd., 7720 Pécsvárad, Hungary
2
Faculty of Agricultural and Environmental Sciences, Institute of Biological Sciences, Szent István University, 2100 Gödöllő, Hungary
3
Faculty of Sciences, Institute of Biology, University of Pécs, 7624 Pécs, Hungary
multidrug-resistant strains (Feiszt et al. 2014). In the last decade complete genome sequences have been obtained for several species of Saccharomonospora genus, however the available genomics information regarding biologically active metabolite production is still underrepresentated compared to other members of Pseudonocardiaceae family. Primycin was fi
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