SBIR Phase II: A computational and experimental platform for the automated design of organisms used in the production of biochemicals

这个小企业创新研究（SBIR）第二阶段项目的更广泛的影响/商业潜力是开发一个平台，快速设计合成生物体来生产生物化学品，这将取代对环境有害，生态效率低下的工业化学工艺。该提案中开发的技术将在合成生物的快速工程方面提供竞争优势，通过发酵生产目前从石油中生产的生物化学品（减少我们的二氧化碳排放量）或从自然物种中提取的生物化学品（减少我们对现有生态系统的税收负担）。这项技术也有可能用于制造药物，并设计新的生物体以提高作物产量，从而帮助解决在不过多利用地球资源的情况下为不断增长的世界人口提供食物的日益严峻的挑战。在商业上，通过应用第一阶段计划开发的技术，化学品将打开目前化学工业无法进入的数十亿美元的市场。SBIR第二阶段项目旨在开发一个平台，将计算酶设计与系统生物学相结合，以创建一个完全集成的系统，用于设计和测试用于生产散装和精细化学品的新型细胞工厂。在第一阶段项目中，该公司与华盛顿大学合作，成功开发了一种高性能软件代码，可快速设计新型代谢途径，以通过中枢代谢产生任何目标化学物质。在第二阶段，该公司将通过以下方式进一步推进这一概念：（1）开发一个高性能的途径优先级模块，以在全基因组模型的背景下估计每个设计的途径产量和对生物体代谢的影响;（2）使用该软件平台来设计用于生产各种具有商业价值且不知道通过发酵产生的特殊化学目标的途径库，规模然后，（3）使用实验筛选装置，将以高通量组装筛选所有拟议途径的DNA，以检测目标化学品的产生。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project is to develop a platform to rapidly design synthetic organisms to produce biochemicals, which will replace environmentally harmful, ecologically inefficient industrial chemical processes. The technology developed in this proposal will provide a competitive edge in the rapid engineering of synthetic organisms to produce biochemicals by fermentation that are currently produced from oil (reducing our CO2 emissions) or extracted from natural species (reducing our taxing load on existing ecosystems). This technology also has the potential to be used for the manufacture of drugs, and to engineer novel organisms to improve crop production and therefore help address the mounting challenges of providing food to a growing world population without tapping too much in Earth's resources. Commercially, the chemicals that will be enabled by application of the technology developed during the Phase I program open up billion dollar markets that are currently inaccessible to the chemical industry. This SBIR Phase II project proposes to develop a platform that combines computational enzyme design with systems biology to create a fully integrated system for the design and testing of novel cell factories for the production of bulk and fine chemicals. During the Phase I project, the company, in collaboration with the University of Washington, has successfully developed a high-performance software code to rapidly design novel metabolic pathways to produce any target chemical from central metabolism. In Phase II, the company will further advance the concept by (1) developing a high-performance pathway prioritization module to estimate each designed pathway yield and impact on organism metabolism in the context of whole-genome models and (2) use the software platform to design libraries of pathways for the production of a variety of specialty chemical targets that are commercially valuable and not known to be produced by fermentation at scale. Then, (3) using an experimental screening setup, the DNA for all the proposed pathways will be assembled screened at high-throughput for detectable production of the target chemicals.