Pilot-scale process sensitivity studies for the scaleup of a fungal fermentation for the production of pneumocandins

Biotechnology and Bioengineering
D J PollardP Salmon

Abstract

The filamentous fungus Glarea lozoyensis produces a novel, pharmaceutically important pneumocandin (B(0)) that is used to synthesize a lipopeptide which demonstrates cidal activity against clinically relevant pathogens. A range of unwanted pneumocandin analogs are also produced by the organism. To maintain the unwanted impurities to acceptable levels upon scaleup, a good understanding of the impact of chemical and physical environment on the cell physiology is required, which benefits downstream processing. Pilot-scale studies were performed to determine the impact of dissolved oxygen, temperature, pH, and carbon dioxide on the process. Experiments included multiple fermenters (up to seven) at 0.07 and 0.8 m(3) scale using single source medium sterilization and inoculum. Gas blending was used to separate effects of dissolved oxygen from agitation. The process was significantly influenced by dissolved oxygen level. The critical dissolved oxygen tension (C(crit)) for growth was below 2% air saturation. The C(crit) for production of pneumocandin B(0) was 20% air saturation, with a significant reduction of the specific production rate below this value. In contrast, low dissolved oxygen levels produced a substantial increase of pneu...Continue Reading

References

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Citations

Mar 7, 2013·Applied Microbiology and Biotechnology·Tamás EmriIstván Pócsi
Oct 15, 2008·Bioprocess and Biosystems Engineering·Beth JunkerNeal Connors
Sep 2, 2003·Journal of Biotechnology·Thomas Hermann
Feb 5, 2010·Journal of Bioscience and Bioengineering·Munekazu KandaHiroyuki Honda
May 10, 2005·Biotechnology and Bioengineering·J Antonio Rocha-ValadezLeobardo Serrano-Carreón
Mar 9, 2007·The Journal of Organic Chemistry·William R LeonardDavid L Hughes

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