Novel bioprocessing strategies for optimization of aerobic fermentation bioreactor performance

用于优化好氧发酵生物反应器性能的新型生物加工策略

• 批准号: RGPIN-2021-02444
• 负责人: MooYoung, Murray
• 金额: $ 2.4万
• 依托单位: University of Waterloo
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=741982
• 关键词: Novel; bioprocessing; strategies; optimization; aerobic

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.

由于近几十年来生物技术的重大进步，人们普遍认识到，基于生物的生产是一种现代的、创新的、可再生的和可持续的方式，具有取代基于石油的生产的潜力。拟议的研究将以设计/开发新的生物处理设施为目标，以便为生物制造目的进行精确的生物系统监测和控制。本课题组新开发的枯草芽孢杆菌和大肠杆菌等多种工程菌株将在传统搅拌槽式和新型波式生物反应器中用于生产L-缬氨酸、透明质酸(HA)、丙酸、聚-3-羟基丁酸酯-3-羟基戊酸酯(PHBV)和病毒样颗粒(VLP)等潜在的蛋白质疫苗候选者。由于相关的生物合成酶和氧气途径的不同敏感性，它们的生物生产在生物反应器培养过程中需要不同程度的曝气。将使用传统的搅拌槽和新型的波式生物反应器来评估曝气需求，并为各种生物产品发酵过程开发最优的曝气生物处理策略。生物制品发酵的不同通风要求将首先根据氧的敏感性和相关生物合成酶和途径的参与来确定。将在两种类型的生物反应器的多个地方安装监测溶解氧水平的微型探头。研制了一种新型细长浸没式气体分散消能器，并将其安装在波浪生物反应器的摇臂袋中，以增强曝气。将建立这些改进设计的生物处理特性，以便对生物反应器发酵过程进行定量评估，以进行集成的机械和生物建模，特别是粘性和高细胞密度发酵。为了在不同的菌种和生物制品发酵条件下广泛应用，将建立增强型生物反应器设计的曝气/搅拌能力与结构和流变特性的数学关联式。拟议研究的成功将促进生物制造领域的科学和工程进展，提高生物加工的经济可行性，并减轻传统化学加工造成的重大环境影响。开发的工程战略和生物工艺可以很容易地转移到加拿大的生物产业，提高加拿大在生物制造方面的技术领先地位。此外，拟议的研究将导致改善甚至新的生物制造企业，为加拿大和其他地方带来社会经济利益。同时进行的多学科研究的高素质人员(HQP)培训预计将导致在现有和新兴的各种生物技术机会中就业。