Carotenoids are C40 natural compounds and a unique class of terpenoids that exhibit a wide spectrum of red to yellow hues in nature. Their diverse biological activities, including antioxidant, anticancer, and anticardiovascular properties, make them sought-after ingredients in the food, nutraceuticals, cosmetics, and aquaculture industries [1]. By 2026, the global carotenoid market size is projected to reach approximately 1.85 billion USD, reflecting a continuous rise in consumer demand [2]. Currently, commercial carotenoid products are primarily derived from plants and microalgae. Yet, challenges such as low extraction yields, susceptibility to weather conditions, and the extensive land and time requirements for the cultivation of these organisms necessitate a more efficient production method [3]. Therefore, microbial-based production has been gaining attention as an alternative carotenoids production platform.

Recent advances in systems metabolic engineering have paved the way for the development of microbial cell factories through the introduction and optimization of heterologous carotenoid biosynthesis pathways into microbial hosts to produce carotenoids [4]. While significant research on carotenoids production using microbial hosts has been performed, hurdles remain in harnessing these engineered strains for industrial applications. These include reaching the titer, yield, and productivity of carotenoids at scales of at least grams per liter and the development of cost-effective downstream processes to ensure the economic viability of industrial-scale production [3]. In this review, we delve into the latest systems metabolic engineering strategies aimed at constructing high-performance carotenoid-producing strains. We specifically focus on metabolic flux enhancement, spatial rearrangement of enzymes, and storage capacity engineering strategies. In addition, we discuss integrated downstream process strategies that can be incorporated during strain development, making carotenoid purification more economically viable.