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，可作为维生素A，强抗氧化剂或保护剂的前体，以应对各种疾病，例如炎症，衰老，白内障，癌症，肥胖，心血管，心血管疾病和神经退行性疾病。由于这些生物学活动，类胡萝卜素对于必须被食物摄入的人类和动物健康至关重要。这种需求对基于类胡萝卜素的产品产生了越来越多的商业兴趣，例如营养素，食物补充剂，着色剂。为了满足市场需求，合成类胡萝卜素用于80-90％的应用中。这些表明可以减少生物活性和健康问题，并且不批准用于人类的消费，但主要用于水产养殖和动物饲料部门的色彩目的。天然类胡萝卜素是通过从天然来源中提取或在微生物中以比有机合成更高的发酵来获得的。在这里，我们将使用贝克的酵母制定一种具有成本效益的策略，用于生产天然类胡萝卜素，旨在替换主要应用中的合成类胡萝卜素，并优化生产以在收支平衡点或更高点上实现产量。我们将开发专门的酵母平台，用于生产astaxanthin和fucoxanthin。我们将整合代谢工程和计算生物学中的最先进方法，以改善酵母中类胡萝卜素酶和重定向代谢物的活性，以便对类胡萝卜素的产生。我们还将操纵类胡萝卜素的运输进出细胞，以实现持续的生产和便捷恢复。最后，我们将通过应用机器学习算法来构建最佳生物反应器参数，细胞生长和生产率以及类胡萝卜素产品谱分析的模型来加速生物处理的开发和优化。酵母制成的类胡萝卜素将在不同层面上对加拿大农业食品领域产生积极影响：1。更健康的水产养殖和动物饲料产品； 2。更便宜，更可用的饮食补充剂和营养； 3。用于进一步生产其他类胡萝卜素的微生物平台； 4。开发基于类胡萝卜素的益生菌的选择。