Fermentation Scale-up Recovery and Purification
Fermentation in bioreactors offer environments that are substantially different from shake flask environments. Strains that are optimized through the design-build-test-learn cycle will be subjected to these unexpected environments and thereby, most often, lead to unanticipated results. At the ABPDU, we have been resolving this disparity between lab-scale and a commercially relevant scale of biomanufacturing. Once optimized at the bioreactor level, we conduct a fermentation to generate the culture needed to optimize downstream recovery and purification operations. Continuous centrifugation, tangential flow filtration, preparative chromatography, liquid-liquid extraction, distillation, etc. are a few such recovery and purification methods that help realize the product in a specification that are amenable to real-world applications. The ABF has substantial experience in working with multiple hosts in this context, several of which are novel. Worked with over 10 hosts including: Rhodosporidium toruloides, Yarrowia lipolytica, Thermoascus aurantiacus, Pichia pastoris, Microbial Communities, E. Coli, S. cerevisiae, etc. The existing capability can help “Test” optimized strains in a bioreactor and use the data to “Learn” and thereby predict scalability of a biological process. In terms of capability, the ABF has access to 2L, 10L, 19L, 50L, and 300L Fermentation Bioreactors; Disc-Stack Centrifuge (~150L/hour), Decanting centrifuge (~6m3/hour), Tangential Flow Filtration (2.5m2 filter area with ~1L/ min capactiy), Liquid-liquid extraction (2L volume column with ~150 mL/min capacity), Preparative Chromatography GE AKTA equipment (~150 mL/min).
References and Additional Information:
Yaegashi J, Kirby J, Ito M, Sun J, Dutta T, Mirsiaghi M, Sundstrom ER, Rodriguez A, Baidoo E, Tanjore D et al: Rhodosporidium toruloides: a new platform organism for conversion of lignocellulose into terpene biofuels and bioproducts. Biotech for Biofuels 2017, 10(1):241.
Schuerg T, Prahl J-P, Gabriel R, Harth S, Tachea F, Chen C-S, Miller M, Masson F, He Q, Brown S et al: Xylose induces cellulase production in Thermoascus aurantiacus. Biotech for Biofuels 2017, 10(1):271.
Kolinko S, Wu Y-W, Tachea F, Denzel E, Hiras J, Gabriel R, Bäcker N, Chan LJG, Eichorst SA, Frey D et al: A bacterial pioneer produces cellulase complexes that persist through community succession. Nature Microbiology 2018, 3(1):99-107.
Lawrence Berkeley National Laboratory
National Renewable Energy Laboratory