Beshanzoides A–D, unprecedented cycloheptanone-containing polyketides from Penicillium commune P-4-1, an endophytic fungus of the endangered conifer Abies beshanzuensis

Abstract

A number of previously undescribed (1–7) and structurally related known (8–17) isobenzofuran-type polyketides were obtained from the fermentation of Penicillium commune P-4-1, an endophytic fungus isolated from the fresh trunk bark of the critically endangered conifer Abies beshanzuensis. Beshanzoides A–D (1–4, resp.) feature a cycloheptanone-containing isobenzofuran ring system hitherto unknown, which might be biosynthesized via two steps of aldol reactions starting from a common co-occurring isobenzofuran-type polyketide as the precursor. The new structures were elucidated by spectroscopic methods, electronic circular dichroism data, and single crystal X-ray diffraction analyses. Beshanzoide E (5) showed antimicrobial activity (MIC: 16 μg mL⁻¹) against Staphylococcus aureus, whereas (±)-strobide A (10) inhibited (MIC: 16 μg mL⁻¹) Candida albicans. Cyclopaldic acid (12) and 3-O-methyl-cyclopaldic acid (13) exhibited inhibitory effects against acetyl-CoA carboxylase 1 (ACC1) with IC₅₀ values of 0.96 and 11.77 μM, respectively. Compound 12 also inhibited (IC₅₀: 7.56 μM) ATP-citrate lyase (ACL).