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Sulfation is a widely used strategy in nature to modify the solubility, polarity, and biological activities of molecules. The enzymes catalyzing sulfation, sulfotransferases (STs), are typically highly specific to a single sulfation site in a molecule. Herein, the identification and characterization of sulfated adipostatins is reported and reveals a novel sulfotransferase, AdpST, which is responsible for di‐sulfation at two sites of adipostatins. The initial bioinformatic analysis in search of adipostatin analogs fromStreptomyces davaonensisDSM101723 identifiesadpSTand a 3’‐phosphoadenosine‐5’‐phosphosulfate (PAPS) biosynthetic cassette, which are co‐clustered with the adipostatin‐encoding type III polyketide synthase. Mono‐ and di‐sulfated adipostatin analogs are discovered in the extracts ofS. davaonensisDSM101723, whereas di‐sulfated bacterial natural products has not been reported. Using a series of in vivo and in vitro experiments, it is confirmed that AdpST is solely responsible for both mono‐ and di‐sulfation of adipostatins, a catalytic activity which has not been identified in bacterial PAPS‐dependent STs to date. It is further demonstrated that the dedicated PAPS biosynthetic cassette improves di‐sulfation capacity. Lastly, it is determined that AdpST shares similarity with a small group of uncharacterized STs, suggesting the presence of additional unique bacterial STs in nature, and that AdpST is phylogenetically distant from many characterized STs.