STTR Phase I: Commercialization of Synthetic Metabolic Valves

这个小企业技术转让（STTR）项目的更广泛的影响/商业潜力将是开发用于生物制造的微生物的生长与产品形成脱钩的技术。 目标是解决目前代谢工程领域的限制，以生产高价值的产品。目前的方法必须平衡生物量增长和产品形成的复杂要求。 此外，筛选规模的进步往往不能转化为商业规模的改进，导致开发时间长且成本高。 该项目将部署一种新型技术平台--合成代谢阀（SMV）--来展示微生物代谢的动态代谢控制，以生产成本优越的上级生物基产品。 这种方法代表了生物化学工程的范式转变。重要的是，这项技术能够实现一套独立于产品的生物工艺的标准化，大大简化和降低目前与生物工艺研发相关的成本和风险。这项STTR第一阶段项目旨在展示合成代谢阀技术的潜力，为快速商业化生物基产品提供创新和颠覆性的方法。 SMV技术通过诱导酶降解与基因沉默技术相结合来实现，用于标准化的两阶段生物过程。与传统方法不同，SMV技术可推广到任何生产途径、任何微生物宿主，并能够实现用于生产多种多样分子的快速代谢工程策略。 重要的是，这项技术提供了强大的微生物宿主的产生，具有无与伦比的跨规模的再现性，从微孔到商业生产。该技术降低了目前与生物基产品生产相关的成本和风险，使产品开发更加快速，成本更低。 为了证明该平台技术，该提议特别针对以成本上级度量生产丙二酸和衍生物。 该计划的成功将证明该技术的可行性，然后可以应用于许多可再生化学品的生产。

The broader impact/commercial potential of this Small Business Technology Transfer (STTR) project will be the development of technology to decouple growth from product formation in microbes used for biomanufacturing. The goal is to address current limitations in the field of metabolic engineering for the production of high value products. Current approaches must balance the complex requirements of both biomass growth and product formation. Furthermore, advancements at screening scale often do not translate to improvements at commercial scale, resulting in long and costly development timelines. This project will deploy a novel technology platform - Synthetic Metabolic Valves (SMV) - to demonstrate the dynamic metabolic control of microbial metabolism for the cost superior production bio-based products. This approach represents a paradigm shift in biochemical engineering. Importantly, this technology enables the standardization of a set of bioprocesses independent of product, greatly simplifying and reducing the costs and risks currently associated with bioprocess R&D.This STTR Phase I project proposes to demonstrate the potential of the Synthetic Metabolic Valve technology to provide an innovative and disruptive approach to rapidly commercialize bio-based products. The SMV technology is enabled by inducible enzyme degradation in combination with gene silencing techniques, utilized in a standardized two-stage bioprocess. Unlike traditional approaches, the SMV technology is generalizable to any production pathway, any microbial host, and enables rapid metabolic engineering strategies for the production of a broad diversity of molecules. Importantly, this technology provides for the generation of robust microbial hosts with unparalleled reproducibility across scale, from micro-well to commercial production. The technology reduces the cost and risk currently associated with production of bio-based products, enabling more rapid and lower-cost product development. To demonstrate this platform technology, this proposal specifically targets production of malonic acid and derivatives at cost superior metrics. Success in this program will demonstrate the feasibility of this technology, which can then be applied to the production of numerous renewable chemicals.