SBIR Phase I: A Biocide/Biocide-Resistant System for Microbial Contamination Control in Biomanufacturing

SBIR 第一阶段：用于生物制造中微生物污染控制的杀菌剂/抗杀菌剂系统

• 批准号: 1843365
• 负责人: Ouwei Wang
• 金额: $ 22.5万
• 依托单位: POW GENETIC SOLUTIONS, INC.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1843365&HistoricalAwards=false
• 关键词: SBIR; Phase; Biocide; Resistant; System

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is to develop technology that will enable robust, contamination-free, continuous biomanufacturing. While biomanufacturing may be one of the most technologically complex and profitable industries, the underlying production process, batch fermentation, has not changed in decades. In theory, continuous fermentation would decrease operational cost and increase production capacity. However, owing to the high risk of contamination, continuous fermentation is considered unreliable and is rarely used. The proposed technology solves this issue and enables contamination-free, continuous fermentation. Successful implementation of continuous fermentation facilitates automated production and paves the way for future technological development in continuous product purification and recovery. The reduced operational cost is essential for the economic viability of bio-based commodity chemicals such as bioplastics, as their market demand depends primarily on their price competitiveness with petroleum-derived counterparts. The proposed technology also eliminates the use of antibiotics in fermentation, which in turn alleviates antibiotic misuse and promotes a positive environmental and health impact. The intellectual merit of this SBIR Phase I project is to explore the feasibility of using a biocide/biocide-resistant system to prevent and treat microbial contamination during continuous biomanufacturing. Microbial contamination in biomanufacturing processes is a major concern, as it results in loss of productivity, time, and money. In addition, it restricts the production mode to slow batch fermentation, and prohibits the implementation of continuous fermentation. The proposed technology solves the contamination problem, as a biocide will inhibit the invading microbial and viral contaminants and a biocide-resistant enzyme will protect the processing hosts. The proposed Phase I research will address the technical challenges by using classical molecular biology and synthetic biology techniques. The first objective is to demonstrate that the proposed technology will provide biocide resistance to bioplastics-producing organisms while inhibiting the outgrowth of contaminants. The second objective is to show that the proposed technology can be used to prevent and treat contamination in continuous fermenters. The final objective is to fine-tune the biocide/biocide-resistant system to demonstrate the technology will not adversely affect the production yield and product quality in continuous fermenters. If successful, future Phase II development will be conducted in pilot and industrial-scale reactors to further optimize the technology.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

这项小型企业创新研究（SBIR）项目的更广泛的影响/商业潜力是开发将实现强大，无污染，连续的生物制造的技术。 尽管生物制造可能是技术上最复杂和有利可图的行业之一，但几十年来的基本生产过程，批处理发酵并没有改变。从理论上讲，连续发酵将降低运营成本并增加生产能力。 但是，由于污染的高风险，连续发酵被认为是不可靠的，很少使用。拟议的技术解决了这个问题，并实现了无污染的连续发酵。连续发酵的成功实施促进了自动生产，并为未来的持续产品纯化和恢复的技术发展铺平了道路。降低的运营成本对于基于生物的商品化学物质（例如生物塑料）的经济可行性至关重要，因为它们的市场需求主要取决于它们与石油衍生的同类产品的价格竞争力。提出的技术还消除了发酵中抗生素的使用，从而减轻抗生素滥用并促进了积极的环境和健康影响。该SBIR I期项目的智力优点是探索使用杀菌剂/耐生菌系统在连续生物制造过程中预防和治疗微生物污染的可行性。生物制造过程中的微生物污染是一个主要问题，因为它会导致生产力，时间和金钱的损失。 此外，它限制了生产模式以减慢批处理发酵，并禁止实施连续发酵。所提出的技术解决了污染问题，因为杀害剂将抑制入侵的微生物和病毒污染物，耐生物剂的酶将保护加工宿主。拟议的I期研究将通过使用经典的分子生物学和合成生物学技术来解决技术挑战。第一个目标是证明所提出的技术将对生物塑料产生生物的生物抗性，同时抑制污染物的生长。第二个目标是证明所提出的技术可用于预防和处理连续发酵罐中的污染。最终的目标是微调抗生物剂/抗生物剂的系统，以证明该技术不会对连续发酵罐的生产产量和产品质量产生不利影响。如果成功，未来的第二阶段开发将在飞行员和工业规模的反应堆中进行进一步优化技术。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛影响的评估审查标准来通过评估来获得支持的。