Terpenoids from the Deep-Sea-Derived Fungus Penicillium thomii YPGA3 and Their Bioactivities.

A chemical study of the ethyl acetate (EtOAc) extract from the deep-sea-derived fungus Penicillium thomii YPGA3 led to the isolation of a new austalide meroterpenoid (1) and seven known analogues (28), two new labdane-type diterpenoids (9 and 10) and a known derivative (11). The structures of new compounds 1, 9, and 10 were determined by comprehensive analyses via nuclear magnetic resonance (NMR) and mass spectroscopy (MS) data. The absolute configurations of 1, 9, and 10 were determined by comparisons of experimental electronic circular dichroism (ECD) with the calculated ECD spectra. Compound 1 represented the third example of austalides bearing a hydroxyl group at C-5 instead of the conserved methoxy in other known analogues. To our knowledge, diterpenoids belonging to the labdane-type were discovered from species of Penicillium for the first time. Compound 1 showed cytotoxicity toward MDA-MB-468 cells with an IC50 value of 38.9 M. Compounds 2 and 11 exhibited inhibition against α-glucosidase with IC50 values of 910 and 525 M, respectively, being more active than the positive control acarbose (1.33 mM).

Austalides V and W, new meroterpenoids from the fungus Aspergillus ustus and their antitumor activities.

Two new austalide meroterpenoids, named austalides V and W (1 and 2), were isolated from the fungus Aspergillus ustus VKM F-4692. Their structures were elucidated by extensive spectroscopic analysis and by comparison with related known compounds. The main structural feature of both compounds is a tetrahydrofuranyl ring (G), a structural fragment, first found in austalides. Austalides V (1) and W (2) were able to inhibit the propagation of prostate and bladder cancer cells; this biologic activity is possibly related to the inhibition of a number of key pathways regulating cell growth and migration.

Austalides S-U, New Meroterpenoids from the Sponge-Derived Fungus Aspergillus aureolatus HDN14-107.

Three new meroterpenoids, named austalides S-U (1-3), were isolated from the culture of a sponge-derived fungus Aspergillus aureolatus HDN14-107, together with eleven known austalides derivates (4-14). Their structures, including absolute configurations, were assigned on the basis of NMR, MS data, and TDDFT ECD calculations. Compound 1 is the first case of austalides with the terpene ring fused to the chroman ring in trans configuration. Compounds 3 and 5 exhibited activities against influenza virus A (H1N1), with IC50 values of 90 and 99 µM, respectively.

Orthoester formation in fungal meroterpenoid austalide F biosynthesis.

Fungal meroterpenoids are important bioactive natural products. Their biosynthetic machineries are highly diverse, and reconstitutions lead to the production of unnatural meroterpenoids. In this study, heterologous gene expression in Aspergillus oryzae and in vitro assays elucidated the biosynthetic pathway of the orthoester-containing fungal meroterpenoid austalide F. Remarkably, the α-ketoglutarate-dependent oxygenase AstB produces the hemiacetal intermediate, and the methyltransferase AstL transfers a methyl group on it to construct the orthoester functionality. This study presents the extraordinary orthoester biosynthetic machinery and provides valuable insights into the creation of unnatural novel bioactive meroterpenoids through engineered biosynthesis. This article is part of the theme issue 'Reactivity and mechanism in chemical and synthetic biology'.