{"doi":"10.1021/jacs.4c09925","title":"Pseudopterosin Biosynthesis: Unravelling a Decades Old Problem in Animal Specialized Metabolism","abstract":"Soft corals are prolific producers of terpenoids, such as pseudopterosins. The exact biosynthetic pathway of these anti-inflammatory diterpene glycosides has eluded the scientific community for decades. Using a forward genetic approach, we have identified, cloned, and expressed the key genes involved in pseudopterosin biosynthesis. We characterized a unique class of multifunctional cytochrome P450 enzymes that catalyze a cascade reaction that produces a nearly mature natural product using a single enzyme. This clarifies the previously proposed biosynthetic pathways to pseudopterosin A and its relatives. The mechanism of the oxidative cascade was probed using in vivo feeding studies in Saccharomyces cerevisiae expressing heterologous coral genes. The cascade produces the pseudopterosin aglycone 7,8-dihydroxyerogorgiaene via elisabethatrienol and its epimer, starting from elisabethatriene. This discovery demonstrates the potential to produce this valuable class of natural products using fermentation.","journal":"Journal of the American Chemical Society","year":2025,"id":517722,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9537,"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":312364,"name":"Eric W. Schmidt","orcid":"0000-0001-5839-694X","position":1,"is_corresponding":false},{"id":850156,"name":"Paul D. Scesa","orcid":null,"position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-19T02:49:04.756302Z","pmid":"39818847","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":[]}