SBIR Phase I: Production of capsaicinoids from microorganisms.

这个小企业创新研究（SBIR）第一阶段项目的更广泛的影响/商业潜力是开发辣椒素的新型生产技术，辣椒素是一种高价值的植物天然产品，可应用于食品，制药和威慑行业。今天，大多数辣椒素都是在辣椒农场附近生产的，这些辣椒农场拥有低成本的劳动力，主要是在印度和中国。辣椒素的供应受到天气变化的影响，导致市场上辣椒素的质量和数量都有很大的波动。所提出的微生物发酵技术提供了几种解决方案。发酵可以在全球范围内部署，可以在几天而不是几个月内满足突然的市场需求。它可以对生产过程进行严格控制，从而提供质量一致的产品。更重要的是，这项技术有潜力以能够扩大市场和开发新应用的价格提供辣椒素。这些技术的商业化不仅将巩固美国在合成生物学研究中的领先地位，而且将在制造具有全球竞争力的产品的同时创造高科技就业机会。该SBIR第一阶段项目是一项提案，旨在证明通过微生物宿主中的发酵生物生产辣椒素。辣椒素目前是通过从辣椒中化学提取而生产的。这一过程效率低，成本高。合成生物学的最新进展提供了将非天然生物化学途径工程化为微生物并使用发酵生产化学品的能力。在这项提案中，辣椒素生物合成途径将被工程化到微生物宿主中，并使用发酵策略进行培养，从而加快上市时间，同时保持强大的经济优势。实验方法利用多变量代谢工程方法，以便以最节省时间和成本的方式获得最佳解决方案。一个功能性辣椒素途径的成功证明将使更复杂的工程努力的天然产物，并将大大提高这一途径在植物中的理解。此外，在这项研究过程中发现的合成生物学工具以及数据科学在合成生物学中的应用有可能迅速加速该领域的创新。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is the development of a novel production technology for capsaicin, a high value plant natural product with applications in the food, pharmaceutical, and deterrent industries. Most capsaicin today is made near chili pepper farms with access to low cost labor, primarily in India and China. The supply of capsaicin is impacted by weather variations resulting in large fluctuations in both quality and quantity of capsaicin on the market. The proposed microbial fermentation technology offers several solutions. Fermentation can be deployed worldwide and can fulfill sudden market demand in days rather than months. It enables tight control over the manufacturing process providing a consistent quality product. More importantly, this technology has the potential to deliver capsaicin at a price that enables market expansion and development of new applications. Commercialization of such technologies will not only solidify the leading role of the United States in synthetic biology research but also will create high tech jobs while making globally competitive products. This SBIR Phase I project is a proposal to demonstrate the bioproduction of capsaicinoids by fermentation in a microbial host. Capsaicin is currently manufactured through chemical extraction from chili peppers. The process is inefficient and expensive. Recent advancements in synthetic biology offer the ability to engineer non-native biochemical pathways into microorganisms and produce chemicals using fermentation. In this proposal, the capsaicinoid biosynthetic pathway will be engineered into a microbial host and cultivated using a fermentation strategy that results in a faster time-to-market while maintaining a strong economic advantage. The experimental approach utilizes multivariate metabolic engineering approaches in order to arrive at optimal solutions in the most time and cost effective way. Successful demonstration of a functional capsaicinoid pathway will enable more complex engineering efforts of natural products and will greatly improve the understanding of this pathway in plants. Moreover, the synthetic biology tools discovered during the course of this research and the application of data science to synthetic biology have the potential to rapidly accelerate innovation in this field.