Liquid fermentation technology optimization of nattokinase: from Lab-scale to Pilot-scale

Area of Science:

• Biotechnology
• Enzyme Engineering
• Industrial Microbiology

Background:

• Nattokinase is a valuable enzyme from natto fermentation.
• Optimizing its production yield and activity is crucial for industrial applications.

Purpose of the Study:

• To optimize and scale up the fermentation process for nattokinase production.
• To develop a stable and controllable process for industrial-scale manufacturing.

Main Methods:

• Optimized liquid fermentation using single-factor and Response Surface Methodology (RSM).
• Implemented fed-batch cultivation in pilot-scale (20 L) and large-scale (200 L) fermenters.
• Developed innovative strategies for oxygen transfer efficiency in large-scale fermentation.

Main Results:

• Achieved 4257 IU/mL nattokinase activity in optimized shake-flask fermentation.
• Reached 23,074 IU/mL in a 20 L fermenter via dynamic oxygen control and feed optimization.
• Attained 21,312 IU/mL in a 200 L fermenter using a novel scale-up strategy.

Conclusions:

• The optimized and scalable fed-batch process significantly enhances nattokinase production.
• The developed methods provide a robust technical solution for industrial nattokinase manufacturing.
• This study lays the groundwork for efficient, large-scale industrial nattokinase production.