Polyphenols represent a diverse group of plant-derived secondary metabolites that have garnered significant attention for their potent bioactive properties and their roles in promoting human health [1]. Renowned for their antioxidant, anti-inflammatory, antimicrobial, and anticancer activities, these compounds are broadly categorized into flavonoids, phenolic acids, stilbenes, curcumin, and lignans [2]. Among these, flavonoids stand out due to their structural complexity and wide-ranging health benefits, including cardiovascular protection, neuroprotection, and anticancer properties [3].

The extensive applications of polyphenols in the pharmaceutical, nutraceutical, and food industries have spurred growing interest in developing sustainable and scalable production methods [4]. While traditional extraction from plant sources remains the primary approach, it is often hampered by limitations, such as low yields, high costs, and environmental concerns linked to large-scale agricultural practices. To overcome these challenges, recombinant biosynthesis has emerged as a promising solution [5]. This innovative approach involves genetically engineering microorganisms like Escherichia coli 6, 7, Saccharomyces cerevisiae 8, 9, and Yarrowia lipolytica 10, 11 to produce polyphenols through the targeted manipulation of biosynthetic pathways, leading to a range of production titers (Table 1).

Among polyphenols, flavonoids have become a focal point in recombinant biosynthesis due to their high industrial demand, intricate biosynthetic pathways, and potential for novel derivative creation [12]. Advancements in microbial production platforms not only address supply constraints but also enable the development of unique compounds with enhanced bioactivities 13••, 14. In this review, we will summarize the biosynthetic pathways of various polyphenols and commonly used metabolic engineering and synthetic biology strategies to improve polyphenol production in microbial hosts.