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

Carotenoids are major constituents of plants, bacteria or yeasts which participate in roles in protection, pigmentation or photosynthesis. They are precursors of vitamin A, powerful antioxidants or protective agents against various ailments, such as inflammation, aging, cataracts, cancer, cardiovascular and neurodegenerative diseases. Due to these biological activities, carotenoids are essential ingredients for human and animal health which must be ingested through food. This need to have a growing commercial interest in products based on carotenoids as food supplements, nutraceuticals, dyes, cosmetics or for aquaculture and animal feed. To meet market demand, synthetic carotenoids are used in 80-90% of applications. They are chemicals from crude petrochemicals and are associated with reduced bioactivities and health problems. Therefore, synthetic carotenoids are not approved for human consumption and are mainly used as dyes in the aquaculture and animal feed industries. Natural carotenoids are obtained by extraction from plants and algae or biological products in microbes by fermentation, processes associated with a higher production cost than organic synthesis. Thus, we will develop a profitable strategy for the production of natural carotenoids using baker's yeast, aiming to replace synthetic carotenoids in major applications. We will reconstruct the biosynthetic pathways of commercially important carotenoids, β-carotene, lutein or astaxanthin, and optimize production to achieve break-even or greater yields. We are also developing strains of yeast dedicated to the future production of arotenoids, which do not yet lend themselves to engineering in non-producing organisms. We will integrate cutting-edge approaches in engineering and computational biology to enhance the activity of carotenogenic enzymes and reorient the necessary metabolites in yeast towards carotenoid production. We also manipulate the transport of carotenoids in and out of cells to allow easy recovery in vegetable oils, thus excluding difficult extraction with organic solvents. Finally, we will accelerate the development and optimization of bioprocesses by applying artificial intelligence algorithms to build a model of optimal bioreactor parameters, growth rates, cell production and analysis of carotenoid product profiles. Yeast carotenoid products will have a positive impact on the Canadian and Quebec agrifood sector at different levels: 1. healthier aquaculture and animal feed products; 2. more available and cheaper dietary supplements and nutraceuticals; 3. Microorganism platforms for the future production of other carotenoids, some of which exhibit unique bioactivities (eg fucoxanthin); 4. options for the development of carotenoid probiotics.