Novel bioprocessing strategies for optimization of aerobic fermentation bioreactor performance

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Due to major biotechnological advances in recent decades, it is well recognized that bio-based production is a modern, innovative, renewable, and sustainable way with potential to replace petro-based production. The proposed research will target design/development of novel bioprocess facilities for precise biosystem monitoring and control for biomanufacturing purposes. Various engineered bacterial strains, including Bacillus subtilis and Escherichia coli, recently developed in our group will be used for the production of value-added chemicals, including L-valine, hyaluronic acid (HA), propionate, poly-3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV), and virus-like particles (VLPs) as potential protein-based vaccine candidates against the COVID-19 virus, in both traditional stirred-tank and novel wave bioreactors. Due to different sensitivities of the relevant biosynthetic enzymes and pathways to oxygen, their bio-based production will require different levels of aeration during bioreactor cultivation. Both traditional stirred-tank and novel wave bioreactors will be used to evaluate the aeration needs and develop the optimal aeration bioprocessing strategies for various bioproduct fermentation processes. Different aeration requirements for bioproduct fermentation will be first determined based on the oxygen sensitivity and involvement of relevant biosynthetic enzymes and pathways. Micro-probes monitoring the level of dissolved oxygen will be installed in multiple places of both types of bioreactors. A novel elongated submerged gas-dispersion sparger will be fabricated and installed in the rocking bag of wave bioreactors for enhanced aeration. Bioprocessing characterization of these enhanced designs will be established to allow quantitative evaluation of bioreactor fermentation processes for integrated mechanistic and biological modeling, especially for viscous and high-cell-density fermentations. Mathematic correlations for the aeration/agitation capabilities and the structural and rheological characteristics of the enhanced bioreactor designs will be developed for extensive application under different strain and bioproduct fermentation conditions. The success of the proposed research will mediate scientific and engineering advances in biomanufacturing, enhance economic feasibility of bioprocessing, and alleviate major environmental impacts caused by traditional chemical processing. The developed engineering strategies and bioprocesses can be readily transferred to the Canadian bioindustry, boosting Canada's technological leadership in biomanufacturing. In addition, the proposed research will lead to improved and even new biomanufacturing enterprises for socioeconomic benefits to Canada and elsewhere. The concurrent highly qualified personnel (HQP) training in multidisciplinary studies is expected to lead to employment in a wide range of present and emerging biotechnology opportunities.