Microbial Transformation of Cycloastragenol and Astragenol by Endophytic Fungi Isolated from Astragalus Species

Abstract

Biotransformation of Astragalus sapogenins (cycloastragenol (1) and astragenol (2)) by Astragalus species originated endophytic fungi resulted in the production of five new metabolites (3,7,10, 12,14) together with 10 known compounds. The structures of the new compounds were established by NMR spectroscopic and HRMS analysis. Oxygenation, oxidation, epoxidation, dehydrogenation, and ring cleavage reactions were observed on the cycloartane (9,19-cyclolanostane) nucleus. The ability of the compounds to increase telomerase activity in neonatal cells was also evaluated. After prescreening studies to define potent telomerase activators, four compounds were selected for subsequent bioassays. These were performed using very low doses ranging from 0.1 to 30 nM compared to the control cells treated with DMSO. The positive control cycloastragenol and 8 were found to be the most active compounds, with 5.2-(2 nM) and 5.1-(0.5 nM) fold activations versus DMSO, respectively. At the lowest dose of 0.1 nM, compounds 4 and 13 provided 3.5and 3.8-fold activations, respectively, while cycloastragenol showed a limited activation (1.5-fold).

Neuroprotective metabolites via fungal biotransformation of a novel sapogenin, cyclocephagenol

“…For metabolite 13 , as in the case of 2 and 6 , an additional oxymethine signal at δ H 3.87 (dd, J = 8.7, 2.5 Hz) was observed, which correlated with a resonance at δ C 65.4 in the HSQC spectrum. Furthermore, the 1 H-NMR spectrum of 13 revealed that one of the 9,19-cyclopropane ring signals (δ H 1.10, H-19a) underwent a significant downfield shift compared to 1 , indicating hydroxylation at the C-11 position as described previously 23 , 26 , 27 . The orientation of C-11(OH) was found to be β based on NOESY cross-peak between H-11 (δ H 3.87) and α-oriented H 3 -30 (δ H 0.84).…”

“…This statement was verified with the HMBC experiment. The hydroxy group at C-12 was determined to be β-oriented for 2 and α-oriented for 6 based on NOESY correlations 26 . Based on this data, the structure of 2 and 6 were identified as 20,25-epoxy-3β,6α,12β,16β,24α-pentahydroxycycloartane and 20,25-epoxy-3β,6α,12α,16β,24α-pentahydroxycycloartane, respectively.…”

Correlation in endophytic fungi community diversity and bioactive compounds of Sophora alopecuroides

“…(2) Endophytic fungi could act as elicitors to induce the expression of host secondary metabolism-related genes and the subsequent production of new metabolites ( Li et al, 2019 ; de Amorim et al, 2020 ). (3) Biotransformation in endophytic fungal metabolites and host metabolites alters plant metabolite composition ( Tian et al, 2014 ; Maggini et al, 2017 ; Ekiz et al, 2019 ). However, the relationship between endophytic fungi of S. alopecuroides and the bioactive compounds of the host has yet to be reported.…”

Assessment of the Endophytic Fungal Composition of Lactobacillus plantarum and Enterococcus faecalis-Fermented Astragalus membranaceus Using Single-Molecule, Real-Time Sequencing Technology

“…High-throughput sequencing in this study may provide a partial answer to previous research demonstrating that the active substances of A. membranaceus , such as Astragalus polysaccharides, flavonoids, saponins, and organic acids, are changed by L. plantarum and E. faecium fermentation ( 3 ). Recently, endophytic fungi originating from Astragalus species have been used for the biotransformation of Astragalus sapogenins ( 21 ). A. chinensis -derived endophytic fungi are verified to be bactericides and fungicides ( 22 ).…”