Bioassay-directed isolation of secondary metabolites from an extract of Penicillium chrysogenum TJ403-CA4 isolated from the medicinally valuable arthropod Cryptotympana atrata afforded five new and 10 known compounds (1-15). All the compounds (except 14) belong to a minor class of highly rigid 6-5-5-5-fused tetracyclic cyclopiane-type diterpenes known to be exclusively produced by members of the Penicillium genus. The structures and absolute configurations of the new compounds (1-5) were elucidated by extensive spectroscopic analyses, including HRESIMS and 1D and 2D NMR, single-crystal X-ray diffraction, and comparison of the experimental electronic circular dichroism data. Compounds 1 and 2 represent the first examples of cyclopianes bearing a C-20 carboxyl group; compound 3 represents the first example of a cyclopiane with a gem-hydroxymethyl group; compound 4 represents the second example of a cyclopiane bearing a hydroxy group at C-7; compound 5 represents the first example of a cyclopiane bearing a hydroxy group at C-8. Compounds 2 and 3 exhibited activity against MRSA, with MIC values of 4.0 and 2.0 μg/mL, respectively. In addition, the structure-antibacterial activity relationship (SAR) of compounds 1-15 is discussed.