{"doi":"10.1002/cbic.202500024","title":"A Bacterial Sulfotransferase Catalyzes an Unusual Di‐Sulfation in Natural Products Biosynthesis","abstract":"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 from Streptomyces davaonensis DSM101723 identifies adpST and 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 of S. davaonensis DSM101723, 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.","journal":"ChemBioChem","year":2025,"id":540814,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9477,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":726844,"name":"Lukuan Hou","orcid":"0009-0007-4531-351X","position":1,"is_corresponding":false},{"id":726846,"name":"Dan Xue","orcid":"0000-0003-4082-1789","position":2,"is_corresponding":false},{"id":1380848,"name":"Mingming Xu","orcid":"0000-0002-8158-2879","position":3,"is_corresponding":false},{"id":1418601,"name":"Katherine S. Holandez-Lopez","orcid":null,"position":4,"is_corresponding":false},{"id":726849,"name":"Jie Li","orcid":"0000-0001-7977-6749","position":5,"is_corresponding":false},{"id":1064497,"name":"Conor Pulliam","orcid":"0009-0009-1512-7956","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-19T02:52:42.901627Z","pmid":"40183316","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}