P96: Challenges in downscaling an industrial fermentation process

Novozymes is a biotechnology company with a strong focus on enzyme production.  Microorganisms are effective producers of enzymes, and Novozymes exploits their productivity through submerged fed-batch fermentation of naturally occurring and recombinant enzymes in microbial hosts such as Bacillus licheniformis and Aspergillus oryzae.  As Novozymes’ business has grown substantially over the last decade, a key to maintaining profitability and managing capital expenditures is the ability to optimize these fermentation processes.

While strain development is a powerful tool to increase productivity of our host organisms, so is more traditional process engineering.  At Novozymes North America in Franklinton, NC, the Global Optimization –US team uses scale-up/scale-down from production to lab as a tool to explore fermentation process in great detail.  Several case studies illustrate ways that scaling down can lead to advances in large scale fermentation processes.  An upgraded agitation system was recently installed, enabling a process to be scaled down effectively and revealing an oxygen transfer limitation in small scale.  Comparison of production-prepared and lab-prepared main media led to identification of a limiting adjunct in the production process.  Poor outgrowth in one host strain was tied to an anomaly in the propagation procedure.