*2.1. Fungal Strain*

Lichen specimens of *Graphis* were collected from Hallasan in Jeju Island, South Korea in 2009. Voucher specimen was deposited in the Korean Lichen Research Institute, Sunchon National University, Korea. The endolichenic fungus EL000327 was isolated with the surface sterilization method [21].

#### *2.2. ITS Sequencing*

EL000327 was cultured for 2–3 weeks on potato dextrose agar (PDA) medium at 25 ◦C. The total DNA was extracted following the manufacturer's instructions from EL000327 using the DNeasy Plant Mini Kit (Qiagen, Hilden, Germany). Universal primers ITS1F (5'- CTTGGTCATTTAGAGGAAGTAA-3') [22] and LR5 (5'-ATCCTGAGGGAAACTTC-3') [23] were amplified with the internal transcribed spacer (ITS) region of the rDNA gene of EL000327 and ITS sequencing was performed as described [5] (Table S1).

#### *2.3. Preparation of Secondary Metabolite Extract of EL000327*

EL000327 was cultured on potato dextrose agar (PDA) medium at 25 ◦C for approximately 2–3 weeks until visible colonies were evident. ELF mycelia grown on agar were cut and inoculated into 200 mL potato dextrose broth (PDB) in 500 mL Erlenmeyer flasks (3 L) and incubated at 25 ◦C in a shaking incubator at 150 rpm for approximately 3–4 weeks. Then, 200 mL ethyl acetate (EA) was added to each flask, and the flask was shaken for approximately 2 h. Each culture was then filtered to separate the filtrate and mycelia. The filtrate was separated into water- and EA-soluble layers by allowing the filtrate to stand in a separating funnel. A total of 5.8 g of crude extracts of EL000327 was obtained by evaporating EA to dryness under a vacuum using a rotary evaporator. The crude extract was dissolved in 100% DMSO for use in experiments.

#### *2.4. Isolation, Purification, and Identification of Chemical Structure of Compound B*

The crude extract (5.8 g) was subjected to open column chromatography purification on a RP C18 flash column by the step gradient elution of methanol/H2O from 20% to 100% of methanol, subsequently, to afford eight fractions (labeled 327-F1 ~ 327-F8). Fraction 327-F2 (360 mg) (H2O:MeOH = 60:40) was purified by reversed-phase HPLC (Phenomenex Luna C-18 (2), 250 × 100 mm, 2.0 mL/min, 5 μm, 100 Å, UV = 254 nm) (Figure S8) using an isocratic solvent system with 47% acetonitrile in water to yield 7β-9α-dihydroxy-1,8(14),15 pimaratrien-3,11-dione (B, 95 mg, purity: 96.7%) as pink oil. 1H NMR (400 MHz, CD3OD) *δ*: 7.25 (d, *J* = 10.4 Hz, 1H), 6.02 (d, *J* = 2.2 Hz, 1H), 5.93 (d, *J* = 10.4 Hz, 1H), 5.74 (dd, *J* = 17.2, 10.4 Hz, 1H), 4.99 (dd, *J* = 17.3, 0.9 Hz, 1H), 4.95 (dd, *J* = 10.4, 0.9 Hz, 1H), 4.40 (m, 1H), 1.29 (s, 3H), 1.20 (s, 3H), 1.18 (s, 3H); 13C NMR (100 MHz, CD3OD) *δ*: 212.1, 206.3, 159.5, 145.4, 141.5, 130.9, 128.8, 69.6, 54.0, 45.7, 45.3, 43.2, 42.9, 33.2, 28.5, 28.1, 22.8, 20.8. HR-FAB-MS *m*/*z* [M+H]<sup>+</sup> 331.1904 (calcd. for C20H27O4, 331.1909) (Figures S6 and S7).

#### *2.5. Cell Culture*

Human CRC cell lines HT29, HCT116, DLD1, Caco2, colon stemness cancer cell line; CSC221, human gastric cancer cell lines; AGS, TMK1, human prostate cancer cell line; RV1, human lung cancer cell line; A549, mouse colon cancer cell line; CT26 and canine kidney epithelial cell line; and MDCK were purchased from the Korean Cell Line Bank (Seoul, Korea). Cells were cultured in DMEM or RPMI culture medium (GenDEPOT, Katy, TX, USA) supplemented with 10% fetal bovine serum (FBS) (GenDEPOT, Katy, TX, USA) and 1% penicillin–streptomycin solution, and incubated in a humidified atmosphere at 37 ◦C in 5% CO2.
