Abstract
The objective of this study was to develop an optimal combination of mineral salts in the fermentation medium for nosiheptide (Nsh) production using statistical methodologies. A Plackett-Burman design (PBD) was used to evaluate the impacts of eight mineral salts on Nsh production. The results showed that among the no-significant factors, CaCO3, and K2HPO4·3H2O had positive effects, whereas FeSO4·7H2O, CuSO4·5H2O, and ZnSO4·7H2O had negative effects on Nsh production. The other three significant factors (Na2SO4, MnSO4·H2O, and MgSO4·7H2O) were further optimized by using a five-level three-factor central composite design (CCD). Experimental data were fitted to a quadratic polynomial model, which provided an effective way to determine the interactive effect of metal salts on Nsh production. The optimal values were determined to be 2.63, 0.21, and 3.37 g/L, respectively. The model also ensured a good fitting of scale-up Nsh batch fermentation with a maximum production of 1501 mg/L, representing a 1.56-fold increase compared to the original standard condition. All these results revealed that statistical optimization methodology had the potential to achieve comprehensive optimization in Nsh fermentation behaviors, which indicates a possibility to establish economical large-scale production of Nsh.
Highlights
Secondary metabolites of microorganisms can serve as good sources of drugs, foods, nutrients, and chemical reagents
Thiopeptide antibiotic scaffolds typically present with several dehydrated amino acids and multiple thiazole or oxazole rings that are highly active against clinically relevant methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Enterococcus faecium (MREF), penicillin-resistant Streptococcus pneumoniae (PRSP), and vancomycin-resistant enterococci (VRE)
The effects of eight mineral salts, CaCO3 (X1), Na2SO4 (X2), K2HPO4·3H2O (X3), MnSO4·H2O (X4), MgSO4·7H2O (X5), FeSO4·7H2O (X6), CuSO4·5H2O (X7), and ZnSO4·7H2O (X8), on Nsh production were investigated by Plackett-Burman design (PBD)
Summary
Secondary metabolites of microorganisms can serve as good sources of drugs, foods, nutrients, and chemical reagents. Nosiheptide (Nsh) isolated from Streptomyces actuosus is a thiopeptide antibiotic belonging to the thiazole heterocyclic peptide antibiotic family [1] It acts on the 50S ribosomal subunit by tightly binding to the complex of 23S rRNA with ribosomal protein L-11 and inhibiting GTP hydrolysis activities by elongation factors [2]. Thiopeptide antibiotic scaffolds typically present with several dehydrated amino acids and multiple thiazole or oxazole rings that are highly active against clinically relevant methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Enterococcus faecium (MREF), penicillin-resistant Streptococcus pneumoniae (PRSP), and vancomycin-resistant enterococci (VRE). For these reasons, research interest in this field has been on the rise over the past years [5,6,7]. Nsh is distinguished from other thiopeptide natural products by an indolic acid macrothiolactone group which forms the smaller B ring and a peculiar
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