Abstract
Pneumocandin B0 is an important antifungal drug precursor produced by filamentous fungus Glarea lozoyensis. The high broth viscosity of cultures of this organism results in lower oxygen solubility and higher energy consumption for agitation and aeration, which mostly caused by the morphologies of filamentous fungi in submerged culture. In this study, the effects of different seed medium nitrogen sources on morphology and fermentation behavior of G. lozoyensis were investigated, and cotton seed powder resulted in small, compact pellets. Moreover, pneumocandin B0 yield in Erlenmeyer flasks were increased by 22.9%. Furthermore, pneumocandin B0 yield in a 50-L fermenter reached 2,100 mg/L and the dissolved oxygen maintained above 30%. Additionally, activities of phosphofructokinase (PFK), isocitrate dehydrogenase (ICDH), glucose 6-phosphate dehydrogenase (G6PDH), and malic enzyme (ME) were increased by 87.5, 50, 41.6, and 10.7%, respectively. This study demonstrates the feasibility and advantages of using cotton seed powder for controlling the fungal morphology and improving the product yield in pneumocandin fermentations.
Highlights
Pneumocandin B0 is a cell-associated lipopeptide produced by the filamentous fungus G. lozoyensis, which is used as an intermediate in the synthesis of caspofungin acetate (Balkovec et al, 2013)
The effect of different seed medium nitrogen sources on the growth of G. lozoyensis was evaluated to understand the relationship with cell growth during cultivation and to increase biomass productivity, improving the economics of pneumocandin B0 production
The maximal pneumocandin B0 yield in the optimized group was 2,100 mg/L, which was increased by 40% with respect to the control group (1,680 mg/L)
Summary
Pneumocandin B0 is a cell-associated lipopeptide produced by the filamentous fungus G. lozoyensis, which is used as an intermediate in the synthesis of caspofungin acetate (Balkovec et al, 2013). It is difficult to scale up the production of pneumocandin B0 to industrial levels due to high medium viscosity and pseudoplastic flow behavior in stirred-tank bioreactors caused by the morphology of G. lozoyensis. Cultures become oxygen-limited and result in low product yield (Pollard et al, 2002). In order to meet the demand of 20% dissolved oxygen (DO) in pneumocandin B0 production, the energy consumption for agitation and aeration is increased during its industrial. Optimized Morphology Increased Fermentation Yield fermentation (Pollard et al, 2007). In addition to reducing energy consumption, DO can be increased by controlling the morphology of filamentous fungus
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