Pilot-scale process development and scale up for antifungal production

Area of Science:

• Biotechnology
• Industrial Microbiology
• Biochemical Engineering

Background:

• Filamentous fungi are sources of valuable bioactive compounds.
• Fermentation processes require optimization for cost-effectiveness and scalability.
• High broth viscosity can impede scale-up of fungal fermentations.

Purpose of the Study:

• To develop and scale up a pilot fermentation process for an antifungal compound.
• To improve fermentation productivity and reduce production costs.
• To overcome scale-up challenges related to broth viscosity.

Main Methods:

• Replaced galactose with lactose, reduced phosphate concentration, and added supplements (glycine, cobalt chloride, trace elements).
• Adjusted initial lactose levels and implemented mid-cycle broth dilution to manage viscosity and nutrient limitations.
• Scaled up the process to 15,000 L working volume using constant aeration rate and peak impeller tip speed.

Main Results:

• Achieved a tenfold increase in peak titers (45 to 448 mg/L) and a tenfold improvement in productivity (3 to 25 mg/L/day).
• Reduced antifoam usage tenfold and improved process robustness.
• Successfully scaled up to 15,000 L by managing broth viscosity through dilution, maintaining target gassed power and mass transfer rates.

Conclusions:

• Optimized fermentation conditions significantly enhanced antifungal compound production.
• Broth viscosity management is critical for successful scale-up of filamentous fungal fermentations.
• The developed process demonstrates a viable strategy for large-scale production of the antifungal compound.