Oxygen supply controls the onset of pristinamycins production by Streptomyces pristinaespiralis in shaking flasks

Abstract

Antibiotics are secondary metabolites, generally produced during stationary phase of growth under different nutritional and hydrodynamic stresses. However, the exact mechanisms of the induction of antibiotics production are still not clearly established. In a previous study, the induction of pristinamycins production by Streptomyces pristinaespiralis as well as product concentrations were correlated with power dissipation per unit of volume (P/V) in shaking flasks. In this study, detailed kinetics of growth, substrate consumption, oxygen transfer rate and pristinamycins production under varying P/V conditions have been obtained and analyzed. Our results showed that higher P/V resulted in a higher concentration of biomass and promoted an earlier nutrient limitation and ultimately an earlier induction of pristinamycins production. The maximal specific growth rate, specific oxygen consumption rate and specific consumption rate of glutamate increased with P/V while influence was less marked with specific consumption rate of glucose, arginine, ammonium ions and phosphate. When oxygen uptake rate (OUR) was limited by free-surface oxygen transfer, pristinamycins production was not detected despite the occurrence of nitrogen and/or phosphate sources limitation. The threshold value for OUR observed was around 25 mmol L(-1) h(-1). This suggested that a limitation in nitrogen and/or phosphate alone was not sufficient to induce pristinamycins production by S. pristinaespiralis pr11. To induce this production, the oxygen transfer had to be non-limiting.

Engineering microbial hosts for production of bacterial natural products

“…Expression of the Vitreoscilla hemoglobin gene ( vgb ) has been shown to significantly improve growth, stress resistance and the production of recombinant proteins and valuable metabolites in many prokaryotic systems, primarily by increasing oxygen uptake and delivery. 170, 171 Consistent with studies demonstrating a positive correlation between antibiotic production levels and oxygen uptake, 172 heterologous vgb expression improved production of pimaricin in Streptomyces gilvosporeus and S. lydicus, 173, 174 actinorhodin in S. coelicolor, 175 and avermectin in S. avermitilis . 176 Expressing a different hemoprotein from Shinorhizobium meliloti has similar effects on metabolite production.…”

Impact of gas–liquid mass transfer on organic acids production by Corynebacterium glutamicum in unbaffled shake flasks

“…Using similar systematic approach and decoupling oxygen transfer and power dissipation, Mehmood et al studied the effect of k L a on the physiological response of filamentous bacterium Streptomyces pristinaespiralis during culture in unbaffled shake flasks. These authors reported a similar relationship linking k L a to the maximal biomass obtained despite the occurrence of two-slope curve that they explained by the oxygen limitation inside the microbial pellets [36]. The effect of oxygen-supply rates on bacterial growth studied in unbaffled flasks with Escherichia coli also exhibited a dependence of maximal amount of biomass to oxygen supply rate even if, unlike in our study, a linear growth was observed for the different conditions in the two first hours [38].…”

“…(10) was 30 %. In previous works, Mehmood et al used this correlation for calculation of the k L a value imposed to bacterial cultures [34][35][36]. However, these estimated values were not validated by experimental measurements.…”

Cyclic Di-GMP Phosphodiesterases RmdA and RmdB Are Involved in Regulating Colony Morphology and Development in Streptomyces coelicolor

“…Interestingly, in several proteobacterial species, including Gluconacetobacter xylinus, E. coli, and Bordetella pertussis (12,62,63), the oxygen concentration affects c-di-GMP synthesis or hydrolysis via heme-containing enzymes. However, studies of the role for oxygen in Streptomyces development have been mainly confined to antibiotic production in industrial cultures, not mechanistic studies (2,37,64). While RmdA is capable of sensing gaseous ligands, its PDE activity is surprisingly nonresponsive to perturbations.…”