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

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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.