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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 (IC 50 6.0 µM, MIC 99 13.9 µM), highlights the importance of the 2-OAc and 3-OAc moieties to the oxandrastin anti-VRE pharmacophore.