Four New Chromones from the Endophytic Fungus Phomopsis asparagi DHS-48 Isolated from the Chinese Mangrove Plant Rhizophora mangle

Abstract

Four new chromones, phomochromenones D–G (1–4), along with four known analogues, diaporchromone A (5), diaporchromanone C (6), diaporchromanone D (7), and phomochromenone C (8), were isolated from the culture of Phomopsis asparagi DHS-48 from Chinese mangrove Rhizophora mangle. Their structures were elucidated on the basis of comprehensive spectroscopic analysis. The absolute configurations of 1 and 4 were assigned on the basis of experimental and calculated electronic circular dichroism (ECD) data, and those of enantiomers 2 and 3 were determined by a modified Mosher’s method and basic hydrolysis. To the best of our knowledge, phomochromenones D–F (1–4) possessing a 3-substituted-chroman-4-one skeleton are rarely found in natural sources. Diaporchromone A (5) showed moderate to weak immunosuppressive activity against T and/or B lymphocyte cells with IC50 of 34 μM and 117 μM.

New polyketides from the liquid culture of Diaporthe breyniae sp. nov. (Diaporthales, Diaporthaceae)

“…Compounds 9 – 13 were respectively identified as phomoxanthones A ( 9 ) and B ( 10 ) ( Isaka et al 2001 ), dicerandrol B ( 11 ) ( Wagenaar and Clardy 2001 ), phomochromenone C ( 12 ) ( Ding et al 2017 ; Wei et al 2021 ), and diaporchromanone C ( 13 ) ( Wei et al 2021 ) by comparison of their HR-ESIMS and 1D and 2 D NMR spectroscopic data (Suppl. material 1 : Figs S65–S99) with those reported in the literature.…”

Epigenetic Manipulation Induced Production of Immunosuppressive Chromones and Cytochalasins from the Mangrove Endophytic Fungus Phomopsis asparagi DHS-48

“…The subsequent keto–enol equilibrium and redox would provide compounds 1 and 2 , referring to the reports made by Rönsberg et al [ 55 ]. Previous feeding experiments with sodium 13 C-labeled acetate by Lösgen et al [ 56 ] in 2007 revealed that a heptaketide precursor is involved in the biosynthesis of 3 and 4 , which are analogues to phomochromenones D-G isolated in our previous study [ 46 ], implying some cryptic post-synthesis modification genes were stimulated by the currently adopted epigenetic manipulation for the production of those metabolites previously unobserved or merely increased sufficiently under epigenetic control to be detected. Cytochalasins 5–11 might rationally share a common biosynthetic precursor as we previously described via polyketide synthase (PKS)/nonribosomal peptide synthetase (NRPS) hybrid machinery [ 38 ].…”

“…The different species belonging to the genus Phomopsis are especially known for producing a wide variety of compounds with pharmacological properties, notably cytotoxic [ 30 , 31 , 32 ], antimicrobial [ 33 , 34 , 35 ], β -site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitory [ 36 ], anti-Tobacco mosaic virus (TMV) [ 37 ] and immunosuppressive activities [ 38 ]. As part of our research on discovering structurally novel and biologically active natural products from mangrove-derived endophytic fungal strains [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ], a strain of Phomopsis asparagi DHS-48 isolated from the fresh root of Rhizophora mangle attracted our attention for the characterization of a series of immunosuppressive chromones [ 46 ] and cytochalasins [ 38 ]. In the present study, in order to tap the metabolic potential of this titled fungal strain, epigenetic manipulation was applied to activate its cryptic secondary biosynthetic pathways.…”

A novel dibenzofuran from endophytic fungus Mycosphaerella nawae preferentially inhibits CD4+ T cell activation and proliferation

“…So far, several secondary metabolites with immunosuppressive activities have been found in endophytic fungi, such as subglutinol A and B, two well-known immunosuppressive agents produced by endophytic Fusarium subglutinans (Lee et al, 1995); peniphenone, conioxanthone A, pinselin and porine B from Penicillium sp. (Liu et al, 2016); rigidiusculamide (−)-oxysporidinone and (−)-4,6′-anhydrooxysporidinone isolated from F. tricinctum (Sun et al, 2018); Fusaspirol A isolated from F. solani (Ariefta et al, 2019); 16-O-deacetylhelvolic acid 21,16-lactone in Aspergillus fumigatus (Xu et al, 2020); diaporchromone A in Phomopsis Asparagi (Wei et al, 2021), as well as (−)-mycousunine enamine from M. nawae in our previously study (Wang et al, 2017). Therefore, endophytic fungi may also be an important source of new immunosuppressants.…”