腸内細菌由来のスルホトランスフェラーゼはアセトアミノフェン硫酸エステルを含む多様なフェノール硫酸エステルに作用する

Sulfonation is one of the two main phase II detoxification pathways in eukaryotes which transforms nonpolar compounds into hydrophilic metabolites. Sulfotransferases catalyze these reactions by transferring a sulfo group from a donor to an acceptor molecule. Human cytosolic sulfotransferases use only 3'-phosphoadenosine 5'-phosphosulfate (PAPS) as a donor to sulfonate a variety of chemicals. Less understood are microbial aryl-sulfate sulfotransferases (ASSTs), which catalyze sulfo transfer reactions, without utilizing PAPS as a donor. Currently, the identity of physiological sulfo donor substrates remains unknown and sulfo acceptor substrates are underexplored. With this study, we aim to understand the potential contribution of a gut microbial enzyme to sulfonation chemistry by uncovering its substrate preferences. Here, we show that a sulfotransferase (Bacteroides vulgatus ASST) from the prevalent gut microbe B. vulgatus (now Phocaeicola vulgatus) is a versatile catalyst that utilizes a wide range of phenolic molecules as substrates that are commonly encountered by the host. With this action, it modulates concentrations of donor phenolic sulfates such as acetaminophen sulfate, dopamine sulfate, p-cresol sulfate, and related compounds in vitro and displays broad acceptor flexibility by sulfonating diverse phenolic compounds, including p-coumaric acid, p-cresol, 4-ethylphenol, tyramine, among others. These findings suggest that gut microbial enzymes like ASSTs may contribute to host detoxification of phenolics, a role previously attributed solely to human sulfotransferases. However, further in vivo studies are necessary to understand the potential contributions of ASSTs to host detoxification processes.