From wells to reactors and back again – scale-up and down for primary and secondary metabolite production

There are many challenges involved in the development of industrial fermentation platforms including reliable and predictive process scale-up, economics, and byproduct minimization.  The type and magnitude of these challenges vary depending on the product and business case.  At Dow AgroSciences, we are developing and optimizing bio-based routes for both primary and secondary metabolites. This talk will highlight some of the challenges that we have faced in these processes using case examples for Spinosad and Propionic Acid to illustrate how we have employed an integrated, multidisciplinary approach to develop solutions. The Spinosad fermentation process uses a filamentous Actinomycete bacterium in a complex media resulting in a viscous, shear-thinning broth that subjects small-scale cultivation to mass transfer limitations that can mask high yielding strains or deliver false positives. Careful analysis of cultivation parameters identified key factors impacting scale-up predictability and improved processes were designed that better predict performance at manufacturing scale using robust experimental designs. In contrast, propionic acid is a primary metabolite and commodity chemical where manufacturing cost is critically important. In developing an economically competitive process, critical scale up factors were identified that lowered by-product formation. Further media development and fermentation process optimization yielded desired productivities and selectivity at a competitive cost position.