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.
Highlights
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)
While S. viridis DSM 43017, S. glauca DSM 43769 and S. cyanea DSM 4410 strains can grow in the fermentation media, none of them were able to produce primycin, no zone of inhibition was detected in the antimicrobial assay (Fig. 1)
On the basis of these innovative technologies, this study reports the result of a comparative structural and functional analysis of S. azurea strains in terms of primycin producing ability
Summary
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. It is well documented that several clinically important bioactive secondary metabolites are synthesized on modular polyketide synthase (PKS) and non-ribosomal peptide synthase (NRPS) enzyme complexes via a conserved thiotemplate mechanism (Du and Lou 2010; Wang et al 2014). Macrolide antibiotics, represented by polyene and non-polyene compounds are one of the most effective antimicrobial agents. Like other guanidine-containing macrocyclic polyketides is synthesized by the bacterial modular type I polyketide synthase pathway.
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