Proanthocyanidins: structure, biosynthesis, regulation, and structure–activity relationships

Proanthocyanidins (PAs) are polyphenolic compounds widely distributed throughout the plant kingdom, playing critical biological and ecological roles, including in seed dormancy and defense. Owing to their powerful antioxidant, protein-binding, and antimicrobial properties, PAs also have broad applications in healthcare, the food industry, and animal nutrition. Here, we examine recent advances in PA research, focusing on their structural diversity, biosynthetic pathways, regulatory networks, and potential applications. All PAs are oligomers or polymers of flavan-3-ol monomers. PA biosynthesis begins with the phenylpropanoid pathway and the production of the starter units (-)-epicatechin and (+)-catechin. Polymerization proceeds by the addition of activated extension units through non-enzymatic mechanisms. PA biosynthesis is facilitated by metabolic compartmentation and precisely regulated by the MYB-bHLH-WD40 core transcriptional complex, which integrates signals from various phytohormones and environmental factors. Despite sharing common building blocks, PAs are structurally extremely complex, due to variations in their constituent monomers, degree of polymerization, linkage patterns, and chemical modifications. These structural features of PAs collectively determine their physicochemical properties and biological activities. Future PA research should focus on key knowledge gaps, including the site(s) of polymerization within the cell, the mechanisms that determine polymer structure, and the precise structure-activity relationships of PAs. Combined with advanced purification technologies and gene editing and synthetic biology strategies, this knowledge will allow the precise biomanufacturing of target PAs, thereby advancing both fundamental research and industrial applications.