Discovery and Characterization of CcrSult1: A Novel Flavonoid Sulfotransferase from the Red Alga <i>Chondrus crispus</i>

Sulfated flavonoids, prevalent in various plants, possess enhanced bioavailability due to the introduction of sulfonate groups, a process catalyzed by flavonoid sulfotransferases (SULTs). These enzymes serve as invaluable tools for exploring the structure-function relationships of sulfated flavonoids and for the preparation of biologically active derivatives. Despite their significance, flavonoid SULTs remain largely unexplored especially for those from marine environment. In this study, we report the discovery of CcrSULT1, the first flavonoid SULT from the red alga<i>Chondrus crispus</i>. Substrate specificity tests revealed that CcrSULT1 exhibits a pronounced chemical selectivity preference for phenolic compounds, particularly flavonoids. More importantly, we discovered that CcrSULT1 may have unique regional selectivity toward mono phenolic hydroxyl groups (e.g., the 4'-OH of kaempferol, a flavonoid aglycone widely distributed in algae and various plants) in substrates, potentially leading to the specific production of monosulfated products. This hypothesis is further supported by the construction of a complex structural model. This study paves the way for the discovery of unknown algal sulfotransferases and provides a biological basis for understanding algal sulfation metabolism and biomass conversion.