Identification of Key Post‐modification Enzymes Involved in the Biosynthesis of Lanostane‐type Triterpenoids in the Medicinal Mushroom Antrodia camphorata.

Article

作者: Bao, Yang‐Oujie ; Tian, Yun‐Gang ; Zhang, Ya‐Qun ; Ye, Min ; Wang, Zi‐Long ; Zhang, Meng ; Ye, Lei ; Wang, Yu‐Qi

AbstractLanostane‐type triterpenoids are important bioactive secondary metabolites of mushrooms, though their biosynthetic study has been challenging due to scattered genes. Herein, the strategies of combining metabolomics and transcriptomics analyses, functional motif blast, and KEGG (Kyoto Encyclopedia of Genes and Genomes) annotation were used to discover three key post‐modification enzymes involved in the biosynthesis of lanostanoids in the medicinal mushroom Antrodia camphorata. The cytochrome P450 enzyme AcCYP4 could generate a Δ7,9(11) diene structure and introduce a 15α‐hydroxy group to the triterpene skeleton. The short‐chain dehydrogenase AcSDR6 could regio‐ and stereo‐ selectively catalyze the dehydrogenation of 3β‐OH to produce 3‐keto triterpenoids, and the catalytic mechanisms were interpreted by crystal structure analysis. AcSMT1 could introduce the methyl group at C‐24 to produce a unique 31‐carbon triterpene skeleton. This work elucidated the major biosynthetic pathway of Antrodia lanostanoids in vitro, and the discovered enzymes could be used to synthesize a series of bioactive triterpenoids.

2025-01-01·Chemistry of Natural Compounds

Triterpenoid Acids of Agaricomycetes (Basidiomycota)

作者: Shakhova, N. V. ; Senik, S. V. ; Shavarda, A. L. ; Kiyashko, A. A.

In this study the screening of 97 species of basidiomycetous fungal strains, belonging to the class Agaricomycetes, was undertaken to search for new producers of triterpenoid acids.Ninety-seven species of basidiomycete fungi from the Komarov Botanical Institute Basidiomycetes Culture Collection (LE-BIN) were analyzed for the presence of triterpenoid acids.Triterpenes were converted into their trimethylsilyl (TMS) ethers by reaction of the aliquot of lipid extract with N,O-bis(trimethylsilyl)trifluoroacetamide (Sigma-Aldrich, USA) (15 min at 100°C) and analyzed by GC-MSusing the gas chromatograph Agilent 7820 with MSD 5975.It was shown that only 15 species produced lanosterol-type triterpene carboxylic acids eburicoic acid (1), trametenolic acid (2), dehydroeburicoic acid (3), and dehydrotrametenolic acid (4).Our screening demonstrated that biosynthesis of triterpenoid acids is a rather rare phenomenon: it was registered in 15 species out of 97.However, producers of triterpenoid acids were found in most orders of the class Agaricomycetes, namely Agaricales, Atheliales, Corticiales, Gloeophyllales, Hymenochaetales, Polyporales, and Russulales but we cannot register that triterpenoid acids in the fruiting bodies of Leccinum aurantiacum, L. scabrum, and L. holopus belonged to the order Boletales.

2024-10-09·Journal of Agricultural and Food Chemistry

Poria cocos Extract Alleviates tPA-Induced Hemorrhagic Transformation after Ischemic Stroke through Regulation of Microglia M1/M2 Phenotypes Polarization

Article

作者: Li, Ruoqi ; Zhang, Shanshan ; Fan, Xiang ; Song, Meiying ; Yu, Wangqin

Delayed thrombolytic therapy with tissue plasminogen activator (tPA), the only FDA-approved drug for ischemic stroke, can cause catastrophic hemorrhagic transformation (HT) after ischemic stroke. However, it remains largely unknown how microglial polarization dynamically changes in HT. Poria cocos is a widely used functional edible fungus in Asia and has been used for more than 2000 years as a food and medicine in China. Our preliminary study found that P. cocos extract (PCE) significantly reduced the volume of cerebral infarction. We performed the effects of PCE on tPA-induced HT in rat models of autologous thromboembolism middle cerebral artery occlusion in vivo and BV-2 cells injured by oxygen-glucose deprivation/reperfusion in vitro. Hemorrhage test and triphenyltetrazolium chloride staining were performed to examine the efficiency of PCE. The expression level of proteins associated with microglia polarization was detected using Western blotting and immunofluorescence staining. Small interfering RNA transfection reveals the regulatory mechanism of PCE on microglia polarization. PCE plus tPA reduced hemorrhage and infarct volumes after ischemic stroke. During tPA-induced HT, M1 microglia increased over time from 3 days onward and remained high for at least 7 days, reaching the peak at 7 days, M2 microglia gradually increased after 3 days and continued to increase for at least 14 days. Furthermore, PCE inhibited the secretion of pro-inflammatory cytokines in M1 microglia and improved the secretion of anti-inflammatory cytokines in M2 microglia, which related to the regulation of the IRF5-IRF4 axis. This current study indicates that PCE alleviates tPA-induced HT after ischemic stroke by modulating microglia M1/M2 phenotype polarization.

100 项与 Dehydroeburicoic acid 相关的药物交易

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