{"doi":"10.1093/plphys/kiac056","title":"Diterpene synthases from<i>Leonurus japonicus</i>elucidate epoxy-bridge formation of spiro-labdane diterpenoids","abstract":"Spiro-9,13-epoxy-labdane diterpenoids are commonly found in Leonurus species, particularly in Leonurus japonicus Houtt., which is a medicinal herb of long-standing use in Asia and in which such spiro-heterocycles are present in at least 38 diterpenoids. Here, through generation of a transcriptome and functional characterization of six diterpene synthases (diTPSs) from L. japonicus, including three class II diTPSs (LjTPS1, LjTPS3, and LjTPS4) and three class I diTPSs (LjTPS5, LjTPS6, and LjTPS7), formation of the spiro-9,13-epoxy-labdane backbone was elucidated, along with identification of the relevant diTPSs for production of other labdane-related diterpenes. Similar to what has been found with diTPSs from other plant species, while LjTPS3 specifically produces the carbon-9 (C9) hydroxylated bicycle peregrinol diphosphate (PPP), the subsequently acting LjTPS6 yields a mixture of four products, largely labda-13(16),14-dien-9-ol, but with substantial amounts of viteagnusin D and the C13-S/R epimers of 9,13-epoxy-labda-14-ene. Notably, structure-function analysis identified a critical residue in LjTPS6 (I420) in which single site mutations enable specific production of the 13S epimer. Indeed, extensive mutagenesis demonstrated that LjTPS6:I420G reacts with PPP to both specifically and efficiently produce 9,13S-epoxy-labda-14-ene, providing a specialized synthase for further investigation of derived diterpenoid biosynthesis. The results reported here provide a strong foundation for future studies of the intriguing spiro-9,13-epoxy-labdane diterpenoid metabolism found in L. japonicus.","journal":"PLANT PHYSIOLOGY","year":2022,"id":269469,"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":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9416,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":932613,"name":"Yaping Mao","orcid":"0000-0002-3828-856X","position":1,"is_corresponding":false},{"id":622984,"name":"Ying Ma","orcid":"0000-0003-2204-0663","position":2,"is_corresponding":false},{"id":254490,"name":"Jian Yang","orcid":"0000-0002-2273-4510","position":3,"is_corresponding":false},{"id":622989,"name":"Baolong Jin","orcid":"0000-0002-3898-2228","position":4,"is_corresponding":false},{"id":933199,"name":"Huixin Lin","orcid":null,"position":5,"is_corresponding":false},{"id":624429,"name":"Jinfu Tang","orcid":null,"position":6,"is_corresponding":false},{"id":622994,"name":"Wen Zeng","orcid":"0000-0001-8149-3764","position":7,"is_corresponding":false},{"id":622992,"name":"Yujun Zhao","orcid":"0000-0001-6687-6652","position":8,"is_corresponding":false},{"id":254495,"name":"Wei Gao","orcid":"0000-0003-3081-9642","position":9,"is_corresponding":false},{"id":254493,"name":"Reuben J. Peters","orcid":"0000-0003-4691-8477","position":10,"is_corresponding":false},{"id":622996,"name":"Juan Guo","orcid":"0000-0002-1327-4428","position":11,"is_corresponding":false},{"id":622985,"name":"Guanghong Cui","orcid":"0000-0001-6072-7867","position":12,"is_corresponding":false},{"id":254494,"name":"Luqi Huang","orcid":"0000-0002-2070-4318","position":13,"is_corresponding":false},{"id":932612,"name":"Jian Wang","orcid":"0000-0002-9386-7986","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-19T00:27:22.602796Z","pmid":"35157086","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":[]}