Perspectives of Bacterial PAPS-Independent Aryl Sulfotransferases for Practical In Vitro Sulfation

PAPS-independent bacterial aryl sulfotransferases (ASTs) do not require the costly and unstable cofactor PAPS like mammalian sulfotransferases. Instead, they use simple aromatic sulfuryl donors. Originally discovered in intestinal bacteria, ASTs display remarkable substrate diversity, catalyzing sulfation of phenols, alcohols, amines, sugars, and polyphenols, including flavonoids and flavonolignans. Among them, AST from Desulfitobacterium hafniense (DhAST) is particularly notable for its stability and broad substrate range. Structural and mechanistic studies reveal that ASTs follow a ping-pong bibi mechanism with transient enzyme sulfation. Recent identification of new ASTs from diverse bacterial species and advances in recombinant expression have broadened the potential of these enzymes for selective and scalable synthesis of sulfated metabolites in vitro. Expanding the available AST library has deepened the understanding of bacterial sulfation pathways and supports their applications in biocatalysis, metabolite synthesis, and production of sulfated bioanalytical standards.