FMSG: Bio: Integrated bioprocess and synthetic biology for future biomanufacturing of industrial products

FMSG：生物：用于未来工业产品生物制造的综合生物过程和合成生物学

• 批准号: 2328215
• 负责人: Shang-Tian Yang
• 金额: $ 50万
• 依托单位: Ohio State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-10-01 至 2025-09-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2328215&HistoricalAwards=false
• 关键词: FMSG; Bio; Integrated; bioprocess; synthetic

Future biomanufacturing of industrial products using novel synthetic biology tools and advanced bioprocesses that convert abundant biomass and waste resources into value-added products with comparable properties will enable circular bioeconomy with affordable energy, economic growth, and innovation in renewable energy and chemicals production. In this project, a multidisciplinary team will collaborate on the research to understand and mitigate bottlenecks limiting continuous production in industrial fermentation. The project team will focus on several non-model microorganisms that are currently used or have enormous potential as cell factories for producing industrial chemicals. The results from this project will guide and accelerate future biomanufacturing of chemicals and fuels and would have large and lasting impacts on the US biomanufacturing industry. The project will benefit the agricultural/rural communities by converting abundant low-value agricultural residues such as corn stover to value-added products and accelerate the growth of a sustainable bioeconomy. Biomanufacturing can also reduce greenhouse gas (GHG) emissions and make a major impact on reducing climate change. This project will also broaden the participation of underrepresented groups and train a diverse range of students and workforce participants with skills to engage in future biomanufacturing. Microbial lifespan and aging are fundamentally important phenomena that will impact industrial fermentation for chemicals production but have not been studied for most microbes including those with important industrial applications. This project focuses on understanding and modulating microbial lifespan genes and regulatory pathways in selected non-model but versatile microbes to produce chemicals and biofuels from renewable resources. This approach will integrate cell recycling to achieve high cell density and high volumetric productivity in continuous or semi-continuous (sequential batch/fed-batch) fermentation. Current production of chemicals and fuels in fermentation is limited by low product titer, productivity or rate, and yield (TRY), poor process stability, short production duration (longevity). These processes are also expensive for industrial application. This project will investigate genes and factors affecting microbial lifespan and aging, which impact cell viability, process performance (TRY), and longevity in industrial fermentation. First, selected microbial strains of industrial interest will be evaluated under different culture and stress conditions to study their effects on growth/fermentation kinetics and culture stability/longevity with population and transcriptomics analyses. The results will be used to identify genes/enzymes contributing to culture heterogeneity, production variability, and limited production duration or longevity. Then, novel synthetic biology tools including recombinase-based state machine (RSM) gene circuits and CRISPR genome engineering, will be used to engineer strains for attaining prolonged lifespan and mediated aging via enhanced stress tolerance. The research hypothesis is that microbial strains with increased lifespan or mitigated aging will be more productive for a longer duration in industrial fermentation. Such strains can be developed through the design-build-test-learn (DBTL) cycle and used in advanced continuous fermentation process with in-situ product recovery, achieving at least 50% improvements in TRY for an extended continuous production period.This Future Manufacturing award was supported by the Division of Molecular and Cellular Biosciences in the Directorate for Biological Sciences.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.

使用新型的合成生物学工具和先进的生物处理对工业产品的未来生物制造，这些工具将丰富的生物量和废物资源转化为具有可比性的增值产品，将使能够具有负担得起的能源，经济增长以及可再生能源和化学物质的创新能够循环生物经济。在这个项目中，一个多学科团队将在研究上进行合作，以了解和减轻瓶颈，从而限制了工业发酵的持续生产。该项目团队将专注于几种非模型微生物，这些微生物目前已使用或具有生产工业化学品的细胞工厂的巨大潜力。该项目的结果将指导和加速化学品和燃料的未来生物制造，并对美国的生物制造业产生巨大的影响。该项目将通过将丰富的低价值农业残留物（例如玉米秸秆）转换为增值产品，并加速可持续生物经济的增长，从而使农业/农村社区受益。生物制造还可以减少温室气体（GHG）的排放，并对降低气候变化产生重大影响。该项目还将扩大代表性不足的群体的参与，并培训各种各样的学生和劳动力参与者，他们的技能可以从事未来的生物制造。微生物的寿命和衰老是从根本上重要的现象，它将影响化学生产的工业发酵，但尚未对包括重要工业应用的大多数微生物进行研究。该项目着重于理解和调节所选非模型但多功能微生物的微生物寿命基因和调节途径，以从可再生资源中生产化学物质和生物燃料。这种方法将在连续或半连续（顺序批处理/饲料批次）发酵中整合细胞回收以实现高细胞密度和高容量生产率。当前发酵中化学品和燃料的生产受到低产品滴度，生产率或速率以及产量（尝试），过程稳定性差，生产持续时间短（寿命）的限制。这些过程对于工业应用也很昂贵。该项目将研究影响微生物寿命和衰老的基因和因素，这会影响细胞活力，过程性能（尝试）和工业发酵的寿命。首先，将在不同的培养和压力条件下评估所选的工业兴趣菌株，以研究其对生长/发酵动力学和培养稳定性/寿命的影响，并通过种群和转录组学分析。结果将用于识别有助于培养异质性，生产变异性以及有限的生产持续时间或寿命的基因/酶。然后，新型合成生物学工具，包括基于重组酶的状态机（RSM）基因电路和CRISPR基因组工程，将用于设计延长寿命和通过增强的胁迫耐受性来实现延长寿命和介导的衰老。研究假设是，寿命增加或减轻衰老的微生物菌株在工业发酵的持续时间更长的持续时间会更有生产力。这种菌株可以通过设计建造测试学习（DBTL）周期来开发，并在高级连续发酵过程中使用，并恢复原地，在延长的连续生产期间的尝试中至少提高了50％的改善。未来的未来制造奖。该奖项由分子和细胞生物科学授予生物学奖，并在生物学上均可申请。通过基金会的智力优点和更广泛的影响评估标准通过评估来支持。