{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hwang J"],"funding":["Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (Conseil de Recherches en Sciences Naturelles et en Génie du Canada)","New Brunswick Innovation Foundation (Fondation de l'innovation du Nouveau-Brunswick)","National Science Foundation (NSF)"],"pagination":["10495"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12647599"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(1)"],"pubmed_abstract":["The inversion of C3 stereochemistry in monoterpenoid indole alkaloids (MIAs), derived from the central precursor strictosidine (3S), is essential for producing pharmacologically important 3 R MIAs and spirooxindoles such as reserpine. While early MIA biosynthesis preserves the 3S configuration, the mechanism underlying C3 inversion has remained unresolved. Here, we identify and biochemically characterize a conserved oxidase-reductase pair in Gentianales: heteroyohimbine/yohimbine/corynanthe C3-oxidase (HYC3O) and C3-reductase (HYC3R), which together invert the 3S stereochemistry to 3 R across diverse substrates. HYC3O and HYC3R are encoded within biosynthetic gene clusters in Rauvolfia tetraphylla and Catharanthus roseus, homologous to a geissoschizine synthase (GS) cluster also uncovered."],"journal":["Nature communications"],"pubmed_title":["Ancient gene clusters govern the initiation of monoterpenoid indole alkaloid biosynthesis and C3 stereochemistry inversion."],"pmcid":["PMC12647599"],"funding_grant_id":["2030871","RAI_2023_054, RPI_2022_002","RGPIN-2020-04133"],"pubmed_authors":["Fleck SJ","Kirshner J","Mai Z","Deslongchamps G","Mann SGA","Blight BA","Silliphant SN","Shahsavarani M","Albert VA","Hwang J","Englehart SA","Gao D","Richardson MB","Lian J","Perley JO","Guo J","Deschenes DAR","Doiron SS","Seveck AD","Qu Y","Calhoun L","Garza-Garcia JJO"],"additional_accession":[]},"is_claimable":false,"name":"Ancient gene clusters govern the initiation of monoterpenoid indole alkaloid biosynthesis and C3 stereochemistry inversion.","description":"The inversion of C3 stereochemistry in monoterpenoid indole alkaloids (MIAs), derived from the central precursor strictosidine (3S), is essential for producing pharmacologically important 3 R MIAs and spirooxindoles such as reserpine. While early MIA biosynthesis preserves the 3S configuration, the mechanism underlying C3 inversion has remained unresolved. Here, we identify and biochemically characterize a conserved oxidase-reductase pair in Gentianales: heteroyohimbine/yohimbine/corynanthe C3-oxidase (HYC3O) and C3-reductase (HYC3R), which together invert the 3S stereochemistry to 3 R across diverse substrates. HYC3O and HYC3R are encoded within biosynthetic gene clusters in Rauvolfia tetraphylla and Catharanthus roseus, homologous to a geissoschizine synthase (GS) cluster also uncovered.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-06-05T16:45:47.105Z","creation":"2026-05-18T03:13:12.46Z"},"accession":"S-EPMC12647599","cross_references":{"pubmed":["41290611"],"doi":["10.1038/s41467-025-65543-z"]}}