Nat Commun
Plant Biochemistry Laboratory, Department of Plant and Environment Sciences, University of Copenhagen, Thorvaldsensvej 40, DK-1871, Frederiksberg C, Denmark.
Published: August 2022
The diterpenoid triepoxides triptolide and triptonide from Tripterygium wilfordii (thunder god wine) exhibit unique bioactivities with potential uses in disease treatment and as a non-hormonal male contraceptives. Here, we show that cytochrome P450s (CYPs) from the CYP71BE subfamily catalyze an unprecedented 18(4→3) methyl shift required for biosynthesis of the abeo-abietane core structure present in diterpenoid triepoxides and in several other plant diterpenoids. In combination with two CYPs of the CYP82D subfamily, four CYPs from T. wilfordii are shown to constitute the minimal set of biosynthetic genes that enables triptonide biosynthesis using Nicotiana benthamiana and Saccharomyces cerevisiae as heterologous hosts. In addition, co-expression of a specific T. wilfordii cytochrome b (Twcytb-A) increases triptonide output more than 9-fold in S. cerevisiae and affords isolation and structure elucidation by NMR spectroscopic analyses of 18 diterpenoids, providing insights into the biosynthesis of diterpenoid triepoxides. Our findings pave the way for diterpenoid triepoxide production via fermentation.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9411204 | PMC |
http://dx.doi.org/10.1038/s41467-022-32667-5 | DOI Listing |
Genes (Basel)
September 2024
Department of Biochemistry, University of California, 900 University Ave, Riverside, CA 92521, USA.
Adv Rheumatol
July 2023
Department of Rheumatology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210027, China.
Introduction/objectives: Systemic lupus erythematosus (SLE) is a classic prototype of the multisystem autoimmune disease and follows a relapsing and remitting course. Triptolide is a diterpene triepoxide extracted from Chinese medicine Tripterygium wilfordii Hook F, with potent immunosuppressive and anti-inflammatory properties. Our previous work observed that triptolide alleviated lupus in MRL/lpr lupus mice with the upregulation of regulatory T cells (Treg) proportion in previous study.
View Article and Find Full Text PDFAnticancer Agents Med Chem
August 2023
Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225009, P.R. China.
Background: Hook F provided the source of the first diterpenoid triepoxide lactone, Triptolide, identified as the primary constituent causing the anticancer activity. So far, it has not been reported whether triptolide has a therapeutic effect on cutaneous squamous cell carcinoma (cSCC).
Objective: This study investigates the triptolide's therapeutic impact on cSCC both in vitro and in vivo and investigates the triptolide's potential involvement in signaling pathways.
Pharm Dev Technol
October 2022
Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, PR China.
Triptolide (TP), a diterpenoid triepoxide, exhibits strong anti-cancer activities, especially against pancreatic cancer, but its clinical application is limited by organ toxicity. TP was combined with diammonium glycyrrhizinate (DG), as a cytoprotective agent, in a novel oral complex lipid emulsion (TP/DG-CLE) to increase the therapeutic index of TP against pancreatic cancer. The emulsion was produced by subjecting phospholipid and active components to high shear conditions using high-pressure homogenisation resulting in droplets of essentially neutral or small positive charge and consistent size below 200 nm.
View Article and Find Full Text PDFNat Commun
August 2022
Plant Biochemistry Laboratory, Department of Plant and Environment Sciences, University of Copenhagen, Thorvaldsensvej 40, DK-1871, Frederiksberg C, Denmark.
The diterpenoid triepoxides triptolide and triptonide from Tripterygium wilfordii (thunder god wine) exhibit unique bioactivities with potential uses in disease treatment and as a non-hormonal male contraceptives. Here, we show that cytochrome P450s (CYPs) from the CYP71BE subfamily catalyze an unprecedented 18(4→3) methyl shift required for biosynthesis of the abeo-abietane core structure present in diterpenoid triepoxides and in several other plant diterpenoids. In combination with two CYPs of the CYP82D subfamily, four CYPs from T.
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