A Sulfotransferase from a Gut Microbe Acts on Diverse Phenolic Sulfate Compounds, Including Acetaminophen Sulfate
Sulfonation is one of the two main phase II detoxification pathways in eukaryotes that transforms non-polar 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 substrate preferences. Here, we show that a sulfotransferase (BvASST) from the prevalent gut microbe Bacteroides 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 has the ability to modulate concentrations of donor phenolic sulfates like acetaminophen sulfate, dopamine sulfate, p-coumaric acid sulfate, indoxyl sulfate, and p-cresol sulfate in vitro. Moreover, we report a large adaptability in the acceptor preferences with the evidence of sulfonation for many biologically relevant phenolic molecules including p-coumaric acid, p-cresol, dopamine, acetaminophen, tyramine, and 4-ethylphenol. These results suggest that such gut microbial enzymes may impact the detoxification of a variety of phenolic molecules in the host, which were previously thought to be solely detoxified via human sulfotransferases. However, further in vivo studies are necessary to understand potential contributions of ASSTs in host detoxification processes.