Yeast Metabolic Engineering for Carotenoid Biosynthesis: Hosts, Pathways, Strategies, and Perspectives

Abstract

Carotenoids are versatile natural pigments with potent antioxidant, anti-cancer, and anti-inflammatory activities, making them valuable ingredients in cosmetics, animal feed, and pharmaceuticals. While traditionally sourced from plants, algae, and microorganisms, conventional extraction methods struggle to meet the rising market demand for natural products. With the rapid advancement of synthetic biology, microbial fermentation has emerged as a scalable and efficient alternative for carotenoid production. This review paper examines four promising yeast platformsPhaffia rhodozyma, Saccharomyces cerevisiae, Yarrowia lipolytica, and Komagataella phaffiifor the production of carotenoids. We systematically outline key modification strategies for the de novo biosynthetic process of carotenoids, primarily including heterologous pathway adaptation, precursor supply enhancement, protein engineering of rate-limiting enzymes, subcellular compartmentalization, and optimization of the fermentation process. Furthermore, we compare the inherent limitations of each yeast chassis and discuss potential solutions to overcome production bottlenecks, thereby providing a strategic roadmap for future strain and process development in support of industrial-scale microbial carotenoid production.