Evaluation of minibioreactors for actinomycetes fermentation for natural product production

One key responsibility of the Dow AgroSciences Bioengineering and Bioprocessing R&D (BBRD) function is to screen novel filamentous microbial strain production of natural products for industrial application.  Strain titer improvements are traditionally realized through both strain improvement and fermentation process development. Scalability and predictability across multiple fermentation platforms is critical when considering inherent co-dependence across platforms to identify and quantify productivity improvements. The strain improvement protocol consists of creating production strain genetic diversity through random mutagenesis, followed by high capacity mutant screening for improved productivity in traditional shake flask format, and statistical titer confirmation of lead strains through experimental replication. Data demonstrates only 10% of strains advanced from shake flask to the bioreactor platform maintained improved productivity. Improved upstream processing quality will increase confidence in lead strains advanced downstream to fermentation platforms alleviating workload waste from the advancement of false positive strains. In 2014 and 2015, researchers conducted a small scale bioreactor technology investigation that could support the filamentous microbial process as a potential solution for the gap in scaling predictability between the strain improvement and fermentation platforms. A total of 10 micro/mini bioreactors with working volumes ranging from 5 to 250-mL were identified as systems of interest based on scaling functionality and throughput capability.  Overall, 3 systems were evaluated on site for fermentation process fit, process performance, operational efficiency and reproducibility.  Upon technology evaluation completion, the TAP Ambr250™ mini bioreactor met all functional and throughput targets chartered by the project team.