A synthetic biology platform for the discovery and commercialization of natural products.

用于天然产物发现和商业化的合成生物学平台。

• 批准号: 537380-2018
• 负责人: Nodwell, Justin
• 金额: $ 4.74万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Collaborative Research and Development Grants
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=691311
• 关键词: synthetic; biology; platform; discovery; commercialization

Specialized metabolites (also known as natural products) are naturally-occurring molecules made by environmental microorganisms that have potent biological activities. Some are beneficial: penicillin, vancomycin, amphoteracin and tetracycline are used as antibiotics to fight bacterial and fungal infections. Conversely, some are harmful. An example is aflatoxin, a potentially fatal toxin produced by food-contaminating Aspergillus species and the causative agent of liver damage and cancer. This proposal concerns specialized metabolites that are of shared interest between the Nodwell laboratory and Toronto Research Chemicals: aflatoxin and pepticinnamin. The Nodwell laboratory is developing pepticinnamin as an anti fungal drug; Toronto Research Chemicals needs a source of aflatoxin to serve as a standard in portable detection kits for aflatoxin. The major limitation in this area of research and commercialization is that the specialized metabolites tend to be produced in very small amounts by the microbes that make them. The molecules themselves are usually too complicated to produce synthetically so this is a major road block. The purpose of this collaborative effort between the Nodwell lab and Toronto Research Chemicals is to overcome this road block by developing methods for producing these molecules at very high levels. To this end we will develop strategies for optimizing the biosynthetic genes for these molecules for higher level expression in living cells. We will engineer these optimized genes into "chassis" strains designed for controlled gene expression. Finally we will develop industrial-scale culture conditions for producing each molecule at a scale appropriate for our research and commercialization needs. This is an initial focus: we regard this work on aflatoxin and pepticinnamin as a trial effort in which we will generate a platform that we can apply to many other compounds of shared mutual interest in the years to come. Our hope is that this will lead to ongoing collaboration.

特化代谢物（也称为天然产物）是由环境微生物产生的天然分子，具有强大的生物活性。有些是有益的：青霉素，万古霉素，阿替拉星和四环素被用作抗生素来对抗细菌和真菌感染。有些是有害的。一个例子是黄曲霉毒素，这是一种由污染食物的曲霉属物种产生的潜在致命毒素，是肝损伤和癌症的病原体。该提案涉及Nodwell实验室和多伦多研究化学品公司共同感兴趣的专门代谢物：黄曲霉毒素和肽菌素。Nodwell实验室正在开发一种抗真菌药物pepticinnamin;多伦多研究化学品公司需要一种黄曲霉毒素来源，作为便携式黄曲霉毒素检测试剂盒的标准。 在这一研究和商业化领域的主要限制是，专门的代谢产物往往是由制造它们的微生物产生的。分子本身通常太复杂，无法合成，所以这是一个主要的障碍。Nodwell实验室和多伦多研究化学品公司合作的目的是通过开发高水平生产这些分子的方法来克服这一障碍。为此，我们将开发优化这些分子的生物合成基因的策略，以便在活细胞中进行更高水平的表达。我们将把这些优化的基因设计成“底盘”菌株，用于控制基因表达。最后，我们将开发工业规模的培养条件，以适合我们的研究和商业化需求的规模生产每个分子。这是一个初步的重点：我们认为这项关于黄曲霉毒素和肽菌素的工作是一项试验性的努力，我们将在其中建立一个平台，在未来几年中，我们可以将其应用于许多其他共同感兴趣的化合物。我们希望这将导致持续的合作。