Abstract
AbstractSulfation, primarily facilitated by sulfotransferases, plays a crucial role in the detoxification pathways of both endogenous substances and xenobiotics, enhancing their water solubility and promoting metabolism and elimination. Traditionally, this bioconversion has been attributed to a family of human cytosolic sulfotransferases (hSULTs) known for their high sequence similarity and dependence on 3’-phosphoadenosine 5’-phosphosulfate (PAPS) as a sulfate donor. However, recent studies have revealed the presence of PAPS-dependent sulfotransferases within gut commensals, indicating that the gut microbiome may harbor a diverse array of sulfotransferase enzymes and may contribute to detoxification processes via sulfation. In this study, we investigated the prevalence of sulfotransferases in the members of the human gut microbiome. Interestingly, we stumbled upon a different class of sulfotransferases, known as aryl-sulfate sulfotransferases (ASSTs). ASSTs have been characterized from a few different prokaryotes includingE. coli. ASSTs do not utilize PAPS which is the default sulfate donor for the human sulfotransferases. Our bioinformatics analyses revealed that the gut microbial genusSutterellapossesses a significant number ofasstgenes, possibly encoding multiple ASST enzymes. Fluctuations in the microbes of the genusSutterellahave been associated with various health conditions. For this reason, we characterized 17 different ASSTs fromSutterella wadsworthensis 3_1_45Bwith bioinformatics. Our findings reveal thatSwASSTs share similarities withE. coliASST but also exhibit significant structural variations and sequence diversity. These differences might drive potential functional diversification and likely reflect an evolutionary divergence from their PAPS-dependent counterparts.
Publisher
Cold Spring Harbor Laboratory