Metabolic Engineering and Synthetic Biology approaches for sustainable and efficient production of carotenoids in yeast

在酵母中可持续高效生产类胡萝卜素的代谢工程和合成生物学方法

• 批准号: 576220-2022
• 负责人: Ignea, CodrutaC
• 金额: $ 5.63万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Alliance Grants
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=744427
• 关键词: Metabolic; Engineering; Synthetic; Biology; approaches

Carotenoids are major constituents in plant, bacteria or fungi that act as precursors of Vitamin A, strong antioxidants or protective agents against various conditions, such as inflammation, aging, cataract, cancer, obesity, cardiovascular and neurodegenerative diseases. Owing to these biological activities, carotenoids are essential for human and animal health that must be ingested by food. This need has generated a growing commercial interest for carotenoid-based products as nutraceuticals, food supplements, colorants. To fulfill the market demands, synthetic carotenoids are used in 80-90 % of applications. These have shown reduces bioactivities and health issues and not approved for human consumption, but mainly used for coloration purposes in aquaculture and animal feed sector. Natural carotenoids are obtained by extraction from natural sources or biologically produced in microbes by fermentation at higher expenses than for organic synthesis. Here, we will develop a cost-effective strategy for production of natural carotenoids using baker's yeast, aiming replace synthetic carotenoids in major applications and optimize production to achieve yields at breakeven point or above. We will develop dedicated yeast platforms for production of astaxanthin and fucoxanthin. We will integrate cutting edge approaches in metabolic engineering and computational biology to improve the activity of carotenogenic enzymes and redirect metabolite fluxes in yeast toward carotenoid production. We will also manipulate carotenoid transport in and out of the cells to enable sustained production and facile recovery. Finally, we will accelerate the bioprocess development and optimization by applying Machine Learning algorithms to construct a model of optimal bioreactor parameters, cell growth and production rates and carotenoid product profile analysis. Yeast-made carotenoids will positively impact the Canadian Agri-food sector at different levels: 1. Healthier aquaculture and animal feed products; 2. Cheaper and more available dietary supplements and nutraceuticals; 3. Microbial platforms for further production of other carotenoids; 4. Options for development of carotenoid-based probiotics.

类胡萝卜素是植物、细菌或真菌中的主要成分，其充当维生素A、强抗氧化剂或针对各种病症（例如炎症、衰老、白内障、癌症、肥胖、心血管和神经退行性疾病）的保护剂的前体。由于这些生物活性，类胡萝卜素是人类和动物健康所必需的，必须通过食物摄入。这种需求已经产生了对类胡萝卜素基产品作为营养品、食品补充剂、着色剂的日益增长的商业兴趣。为了满足市场需求，80- 90%的应用中使用合成类胡萝卜素。这些已被证明会降低生物活性和健康问题，并且未被批准用于人类消费，但主要用于水产养殖和动物饲料部门的着色目的。天然类胡萝卜素是通过从天然来源中提取或通过发酵在微生物中生物生产而获得的，其成本高于有机合成。在这里，我们将开发一种具有成本效益的策略，用于使用面包酵母生产天然类胡萝卜素，旨在取代主要应用中的合成类胡萝卜素，并优化生产，以达到盈亏平衡点或以上的产量。我们将开发生产虾青素和岩藻黄质的专用酵母平台。我们将整合代谢工程和计算生物学的尖端方法，以提高类胡萝卜素酶的活性，并将酵母中的代谢物通量重新定向到类胡萝卜素生产。我们还将操纵类胡萝卜素进出细胞的运输，使持续生产和容易恢复。最后，我们将通过应用机器学习算法构建最佳生物反应器参数，细胞生长和生产速率以及类胡萝卜素产物分布分析的模型来加速生物过程的开发和优化。酵母制造的类胡萝卜素将在不同层面上对加拿大农业食品部门产生积极影响：1。更健康的水产养殖和动物饲料产品; 2.更便宜和更容易获得的膳食补充剂和保健品; 3.进一步生产其他类胡萝卜素的微生物平台; 4.开发类胡萝卜素益生菌的选择。