Abstract
The ethyl acetate extract of an ISP-2 agar cultivation of the wasp nest-associated fungus Penicillium sp. CMB-MD14 exhibited promising antibacterial activity against vancomycin-resistant enterococci (VRE), with a bioassay guided chemical investigation yielding the new meroterpene, oxandrastin A (1), the first andrastin-like metabolite with an extra oxygenation at C-2. A culture media optimisation strategy informed a scaled-up rice cultivation that yielded 1, together with three new oxandrastins B–D (2–4), two known andrastins C (5) and F (6), and a new meroterpene of the austalide family, isoaustalide F (7). Structures of 1–7 were assigned based on detailed spectroscopic analysis and chemical interconversion. A GNPS molecular networking analysis of the rice cultivation extract detected the known austalides B (8), H (9), and H acid (10), tentatively identified based on molecular formulae and co-clustering with 7. That the anti-VRE properties of the CMB-MD14 extract were exclusively attributed to 1 (IC50 6.0 µM, MIC99 13.9 µM), highlights the importance of the 2-OAc and 3-OAc moieties to the oxandrastin anti-VRE pharmacophore.
Highlights
The widespread emergence of antibiotic resistance is seriously undermining the capacity of modern antibiotics to protect against infectious disease
Turning our attention to the need for new antibiotic classes, and prompted by promising antibacterial activity against vancomycin-resistant enterococci (VRE), this current report describes an investigation into the antibacterial natural products of the mud dauber wasp nest-derived Penicillium sp
Comparison of the 1D Nuclear magnetic resonance (NMR) data for 7 (Tables 3 and S8; Figures S29 and S30) with 11 suggested the presence of a C-15 2◦-OH in 7 (H-15 δH 3.71, dd, 10.5, and 5.9; C-15 δC 68.8) as opposed to the C-16 2◦-OH in 11. This hypothesis was confirmed by 2D NMR correlations, which together with diagnostic ROESY correlations established the structure and relative configuration (Figure 7), with the absolute configuration for isoaustalide F (7) assigned on the basis of comparable experimental Electronic Circular Dichroism (ECD) spectra and specific rotations ([α]D = −43), with those reported for the known austalides F ([α]D = −57.7) [11]
Summary
Citation: Elbanna, A.H.; Khalil, Z.G.; Capon, R.J. Oxandrastins: Antibacterial Meroterpenes from an Australian Mud Dauber Wasp Nest-Associated Fungus, Penicillium sp. CMB-MD14. Molecules 2021, 26, 7144. https://doi.org/10.3390/ molecules26237144 Received: 9 November 2021 Accepted: 24 November 2021 Published: 25 November 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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