Building Synthetic Yeast Factories to Produce Fat-soluble Antioxidants

Fat-soluble antioxidants play a vital role in protecting the body against oxidative stress and damage. The rapid advancements in metabolic engineering and synthetic biology have offered a promising avenue for economically producing fat-soluble antioxidants by engineering microbial chassis. This review provides an overview of the recent progress in engineering yeast microbial factories to produce three main groups of lipophilic antioxidants: carotenoids, vitamin E, and stilbenoids. In addition to discussing the classic strategies employed to improve precursor availability and alleviate carbon flux competition, this review delves deeper into the innovative approaches focusing on enzyme engineering, product sequestration, subcellular compartmentalization, multistage fermentation, and morphology engineering. We conclude the review by highlighting the prospects of microbial engineering for lipophilic antioxidant production. [Display omitted] •Enzyme matching/engineering and metabolite channeling enhance microbial production.•Product sequestration is key to improving the production of lipophilic compounds.•Subcellular compartmentation enhances pathway efficiency and reduces competition.•Decoupling production from growth reduces cellular stress and boosts productivity.•Morphology engineering plays a crucial role in strains displaying dimorphic features.