SBIR Phase I: Volatile gene expression reporters for use during fermentation

这个小企业创新研究第一阶段项目建议开发一套新颖、通用的测量工具，用于发酵和代谢工程的放大。这些工具将基于气味剂的生产，并能够实时监测发酵过程中的基因表达水平。代谢工程在包括纤维素生物燃料、治疗药物生产和生物基、环境友好型化学品制造在内的一系列重要应用中具有巨大的前景。但任何这样的项目都要求表达相关生物合成途径的工程生物体从实验室规模的培养扩大到大规模的商业发酵。这不是一项简单的任务，而且每个项目都不同，因为每种工程菌株所需的发酵条件不同。新的测量工具将能够更详细地量化发酵过程中的细胞状态，以便菌株和途径优化更加知情。这项研究的更广泛的影响是能够为大规模发酵提供更明智的菌株优化，从而降低生物基制造业的研发成本。随着人们对清洁技术和石油制造替代品的兴趣日益浓厚，许多新公司和现有公司正在进入生物工程和生物制造行业。然而，所有这些公司都面临着一个共同的障碍，即将其燃料、特种化学品或生物材料的生产规模扩大到商业规模。这些公司花费了大量的研发资金和时间来优化发酵过程中的途径产量。例如，杜邦公司花了7年时间和4亿美元扩大了1,3-丙二醇的微生物生产规模。杰伊·凯斯林（Jay Keasling）是一家领先的合成生物学公司Amyris Biotechnologies的创始人，他报告说，Amyris公司95%的时间都在试图发现和消除其工程代谢途径中各成分之间的意外相互作用。降低生物燃料和工业生物技术行业的研发成本，将为环保、生物基生产解决方案开辟新的应用领域。该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。

This Small Business Innovation Research Phase I project proposes to develop a set of novel, versatile measurement tools for use during fermentation and scale-up in metabolic engineering. The tools will be based on the production of odorants and enable real-time time monitoring of gene expression levels during fermentation. Metabolic engineering holds great promise for enabling a range of important applications including cellulosic biofuels, therapeutics production, and bio-based, environmentally-friendly chemical manufacturing. But any such project requires that an engineered organism expressing the relevant biosynthetic pathway be scaled up from lab-sized cultures to large-scale commercial fermentation. This is not a straightforward task, and is different for every project, because the fermentation conditions required for each engineered strain are different. The new measurement tools will enable more detailed quantification of cell state during fermentation so that strain and pathway optimization is more informed.The broader impacts of this research are to enable more informed strain optimization for large-scale fermentation thereby reducing R&D costs for the bio-based manufacturing industry. With the growing interest in clean technology and alternatives to petroleum-based manufacturing, many new companies and existing companies are moving into the bioengineering and biomanufacturing industries. However, all of these companies face a common hurdle of scaling up production of their fuel, specialty chemical or biomaterial to commercial scale. The companies spend significant R&D money and time optimizing pathway yield during fermentation. For example, Dupont took 7 years and $400M to scale-up microbial production of 1,3-propanediol. Jay Keasling, a founder of Amyris Biotechnologies, a leading synthetic biology company, reported that Amyris spends 95% of their time trying to find and eliminate unintended interactions between components in their engineered metabolic pathways. Reducing the R&D costs in the biofuels and industrial biotechnology industries would open up new application areas to environmentally-friendly, bio-based production solutions.This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).