SBIR Phase I: Software and Services to Enable Metabolic Flux Analysis in Biotechnology Research

这个小企业创新研究（SBIR）第一阶段项目的更广泛的影响/商业潜力是开发新的软件技术来评估细胞代谢，这对于优化生物化学、药物和食品的细胞制造至关重要。同样的技术也可用于药物发现和治疗应用，以治疗代谢性疾病，如癌症或糖尿病。通过提供细胞代谢率的关键信息，提出的技术将使商业研究人员能够识别限制生产的缓慢途径或将能量和原材料从产品中转移的浪费途径，从而允许快速合理的工程来改善生物制造的细胞。预计这些代谢分析工具的扩大使用将通过加快生物技术和制药行业的产品和工艺开发，对美国经济产生广泛的影响。通过将这些分析服务产品化，它还可以建立更具可扩展性和可重复性的业务策略。SBIR一期项目建议开发软件工具和模块化分析，使商业研究人员能够将13C通量分析完全集成到他们的代谢工程工具箱中。这项技术提供了活细胞内代谢途径活动的直接读数，否则不可能直接测量。然而，迄今为止，大多数13C通量研究都是在学术实验室进行的，在工业环境中受到的关注有限。这在很大程度上是由于缺乏实验和计算相结合的专业知识，无法在工业中有效地进行13C通量研究。这项研究具有创新性，因为它标志着将13C通量分析从学术实验室空间转移到商业空间的重要一步。本提案的总体目标将通过追求以下具体目标来实现：1)开发与当前商业研究软件标准一致的通量分析软件，2)开发标准化，高通量，模块化通量分析，用于量化工业细胞工厂的代谢。这项研究的关键成果将是重要的，因为它将产生一个能够加速实验、分析和计算工作流程的集成平台，以扩大13C通量分析在工业研究中的应用。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is to develop novel software technologies to assess cellular metabolism, which is critical for optimizing cell-based manufacturing of biochemicals, drugs, and foods. The same technology also may be used for drug discovery and therapeutic applications to treat metabolic diseases such as cancer or diabetes. By providing critical information about cellular metabolic rates, the proposed technology will enable commercial investigators to identify slow pathways that limit production or wasteful pathways that divert energy and raw materials away from the product, thus allowing for quick and rational engineering to improve cells for biomanufacturing. It is anticipated that the expanded use of these metabolic analysis tools will have a widespread impact on the US economy through enabling faster product and process development in the biotechnology and pharmaceuticals industries. It also will enable the establishment of a more scalable and repeatable business strategy by productizing these analysis services. This SBIR Phase I project proposes to develop software tools and modular assays that will enable commercial investigators to fully integrate 13C flux analysis into their metabolic engineering toolbox. This technology provides direct readouts of metabolic pathway activities inside of living cells, which are otherwise impossible to directly measure. However, the majority of 13C flux studies to date have been performed in academic labs and have received limited attention in industrial settings. This is largely due to the lack of combined experimental and computational expertise to effectively perform 13C flux studies in industry. This research is innovative because it marks an important step in moving 13C flux analysis outside of the academic lab space and into the commercial space. The overall objective of this proposal will be accomplished by pursuing the following specific aims: 1) Develop flux analysis software consistent with current standards of commercial research software, and 2) develop standardized, high-throughput, modular flux assays for quantifying the metabolism of industrial cell factories. The key outcomes of this research will be significant, as it will produce an integrated platform capable of accelerating the experimental, analytical, and computational workflows necessary to expand the application of 13C flux analysis to industrial research.