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: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=747170
• 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，人们普遍认为生物基生产是一种现代、创新、可再生和可持续的方式，有可能取代石油基生产。拟议的研究将针对新型生物工艺设施的设计/开发，用于生物制造目的的精确生物系统监测和控制。我们团队最近开发的各种工程菌株，包括枯草芽孢杆菌和大肠杆菌，将用于生产增值化学品，包括L-缬氨酸，透明质酸（HA），丙酸盐，聚-3-羟基丁酸酯-co-3-羟基戊酸酯（PHBV）和病毒样颗粒（VLP），作为针对COVID-19病毒的潜在蛋白质疫苗候选物，在传统的搅拌槽和新型波生物反应器中。由于相关生物合成酶和途径对氧气的敏感性不同，它们的生物基生产在生物反应器培养期间将需要不同水平的通气。传统的搅拌槽和新型波生物反应器将被用来评估曝气需求，并开发各种生物产品发酵过程的最佳曝气生物处理策略。生物产品发酵的不同通气要求将首先基于氧敏感性和相关生物合成酶和途径的参与来确定。监测溶解氧水平的微探针将安装在两种类型生物反应器的多个位置。一种新型的细长浸没式气体分散分布器将被制造并安装在波浪生物反应器的摇摆袋中以增强曝气。将建立这些增强设计的生物加工表征，以允许对生物反应器发酵过程进行定量评价，用于综合机械和生物建模，特别是粘性和高细胞密度发酵。将开发用于不同菌株和生物产品发酵条件下的广泛应用的增强生物反应器设计的通气/搅拌能力和结构和流变特性的数学相关性。拟议研究的成功将介导生物制造的科学和工程进步，提高生物加工的经济可行性，并减轻传统化学加工造成的主要环境影响。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的技术领导地位。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效益。在多学科研究的并行高素质人才（HQP）培训预计将导致在广泛的现有和新兴的生物技术机会就业。