Benzyl Furanones and Pyrones from the Marine-Derived Fungus Aspergillus terreus Induced by Chemical Epigenetic Modification

Abstract

Chemical epigenetic modification on a marine-derived fungus Aspergillus terreus RA2905 using a histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), resulted in a significantly changed metabolic profile. A chemical investigation of its ethyl acetate (EtOAc) extract led to the isolation of a racemate of benzyl furanone racemate (±)-1, which further separated chirally as a pair of new enantiomers, (+)- and (−)-asperfuranone (1), together with two new benzyl pyrones, asperpyranones A (2) and B (3). Their structures were elucidated by analysis of the comprehensive spectroscopic data, including one-dimensional (1D) and two-dimensional (2D) NMR, and HRESIMS. The absolute configurations were determined by electronic circular dichroism (ECD) calculation and single-crystal X-ray crystallographic experiment. The structures with benzyl furanone or benzyl pyrone skeletons were discovered from natural products for the first time. Compounds (±)-1, (+)-1, (−)-1, and 2 displayed the antifungal activities against Candida albicans with MIC values of 32, 16, 64, and 64 μg/mL and PTP1B inhibitory activities with the IC50 values of 45.79, 17.32, 35.50, and 42.32 μM, respectively. Compound 2 exhibited antibacterial activity against Pseudomonas aeruginosa with the MIC value of 32 μg/mL.

Enhanced production of terrein in marine-derived Aspergillus terreus by refactoring both global and pathway-specific transcription factors

“…And, a variety of secondary metabolites, including butyrolactones, thiodiketopiperazine, and benzyl furanones and pyrones were isolated from the marine-derived A . terreus RA2905 [ 24 , 25 ]. To determine the effect of terR overexpression, stuA deletion and combined mutation on the biosynthesis of other secondary metabolite, the extracts of OE terR , Δ stuA or Δ stuA ::OE terR and WT were analyzed by LC–MS/MS (Fig.…”

Marine natural products

“…158 Other A. terreus strains were the source of a dihydrobenzofuran-phenyl acrylate 362 , 159 butenolide derivative 363 , 160 benzyl furanones 364 and 365 and pyrones 366 and 367 . 161 Meroterpenoids 368 and 369 , each with a novel 6/6/6/6/5 ring system, and terretonin derivative 370 were obtained from a gastropod mollusc-derived strain of A. terreus . 162 Another A. terreus strain has yielded a wide range of aromatic metabolites including 371–379 , of which aspernolide C 372 , astepyrazinoxide 376 , astepyrazinol A 377 and 4-hydroxy-3-(3-methylbut-2-enyl)benzaldehyde 379 were known terrestrial but new MNPs.…”

Cryptic Metabolites from Marine-Derived Microorganisms Using OSMAC and Epigenetic Approaches

“…Compound 254 also exhibited good antibacterial activity against Pseudomonas aeruginosa. None of the isolated compounds showed significant cytotoxic activity [104].…”