Enhancement of daptomycin production in Streptomyces roseosporus LC-51 by manipulation of cofactors concentration in the fermentation culture

Abstract

The effects of eight cofactors of enzymes on daptomycin production were investigated in this work, which included nicotinic acid (VPP), riboflavin (VB 2 ), heme, thiamine (VB 1 ), biotin (VH), cyanocobalamin (VB 12 ), tetrahydrofolic acid (THF) and pyridoxal 5-phosphate (VB 6 ). The dry cell weight (DCW), consumption of glucose, and daptomycin production were obviously improved when proper amount of exogenous cofactors were supplemented in the medium. The effects of heme, THF, VB 12 and VB 6 on daptomycin production were especially notable. The daptomycin yield enhanced 363, 104, 53 and 46%, respectively, when optimized amount of these four cofactors were supplemented in the broth. Moreover, the daptomycin yield further increased to 632 mg/l, which was over 4.5-fold higher than that of the control (without cofactors), at 132 h in a 7.5-l fermenter, by supplementation all of the eight cofactors at optimized concentrations (VPP 4 mg/l, VB 2 0.5 mg/l, heme 9 mg/l, VB 1 0.4 mg/l, VH 0.1 mg/l, VB 12 0.04 mg/l, THF 6 mg/l and VB 6 0.4 mg/l). Further, the effects of cofactors on the corresponding key enzymes and important intracellular metabolites were studied in order to elucidate the mechanism of enhancement of daptomycin production by manipulation of cofactors concentration in the fermentation culture. It is suggested that this strategy for increasing the daptomycin production in Streptomyces roseosporus LC-51 by manipulation of cofactors concentration in the fermentation culture may provide an alternative approach to enhance the production of metabolites in other Streptomyces.

Carbohydrate Metabolite Pathways and Antibiotic Production Variations of a Novel Streptomyces sp. M3004 Depending on the Concentrations of Carbon Sources

“…The result is in agreement with the findings of Kreig and Holt [43], who reported that fermentable carbon sources by Streptomycetes induced both growth and antibiotic production. The above results also indicated the relationship between the antibiotic production and both glycolysis and pentose phosphate pathways, which are known to be aerobically NADH-, ATP-, and NADPHgenerating systems, respectively [44].…”

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“…N-decanoic acid was fed at 48 h after inoculation (0.2 g/l). All experiments were done in triplicate 10 .…”

Improved production of Daptomycin in an airlift bioreactor by morphologically modified and immobilized cells of Streptomyces roseosporus

“…Cofactors were added to the sterile culture medium after aseptic filtration. Eight cofactors were added which included nicotinic acid(4 mg/l), riboflavin(0.5 mg/l), heme(9 mg/l), thiamine(0.4 mg/l), biotin(0.1 mg/l), cyanocobalamin(0.04 mg/l), tetrahydrofolic acid(6 mg/l) and pyridoxal 5-phosphate(0.4 mg/l) (Yu et al 2011 ). As for the airlift bioreactor, the pH was automatically controlled at 7.0 with 8 M NaOH solution and the aeration speed of 1 v/v/m for 6 days.…”