Stereodivergent Hydroxylation of Berkeleylactones by Penicillium turbatum

Abstract

Penicillium turbatum has previously been reported to produce A26771B, a 16-membered macrocyclic polyketide with activity against Gram-positive bacteria, mycoplasma, and fungi, as well as the structurally related compounds berkeleylactone E and berkeleylactones I−O. In this work, large-scale cultivation of P. turbatum NRRL 5630 on rice yielded seven new berkeleylactone analogues, berkeleylactone E methyl ester, 14-epi-berkeleylactone F, berkeleylactones P−R, 12-epi-berkeleylactone Q, and 13-epiberkeleylactone R, and six previously reported analogues, A26771B and berkeleylactones E−G and J−K. The structures of the berkeleylactones were elucidated by detailed analysis of spectroscopic data, molecular modeling, and comparison with literature values. Interestingly, six of the berkeleylactone analogues were isolated as pairs of hydroxy epimers, highlighting how Nature can exploit stereodivergence in biosynthetic pathways to increase chemical diversity. The genome of P. turbatum was sequenced, and a putative gene cluster (bekl) responsible for the biosynthesis of the berkeleylactones was identified. The new berkeleylactone analogues exhibited no significant biological activity against a panel of bacteria, fungi, the parasite Giardia duodenalis, or NS-1 murine myeloma cells, suggesting a hitherto undiscovered biological role.

Geministatins: new depside antibiotics from the fungus Austroacremonium gemini

“…3). This confirmed the position of the double bonds to be Δ 15,16 and Δ 18,19 and thus completed the structure elucidation of 1. Geministatin B (2) was isolated as a white powder.…”

“…A. gemini was cultivated on a range of agars [glycerol casein agar (GCA), Czapek's agar (CZA), oatmeal agar (OMA), malt extract agar (MEA) and yeast extract sucrose agar (YES)] and grains [cracked wheat (BL), pearl barley (PB), jasmine rice (JR)] commonly used for cultivation of fungi with a broad saprophytic diet [16]. HPLC analysis of the cultures revealed consistent secondary metabolite profiles across the media (Fig.…”