*3.2. Fungal Material*

The endophytic fungi *Phomopsis asparagi* DHS-48 was isolated with a PDA medium from the fresh root of the mangrove plant Rhizophora mangle, collected in October 2015 in Dong Zhai Gang-Mangrove Garden on Hainan Island, China. The strain was isolated under sterile conditions from the inner tissue of the root, following an isolation protocol described previously [57], and the fungi (strain no.DHS-8) was identified using a molecular biological protocol via the DNA amplification and sequencing of the ITS region (GenBank Accession no.MT126606). A voucher strain was deposited at one of the authors' laboratories (J.X.).

#### *3.3. Epigenetic Manipulation and Culture Condition*

For the epigenetic manipulation experiments, fungal mycelia and spores were initially inoculated onto Petri dishes containing potato dextrose agar (PDA) at 28 ◦C for 5 days. Then, a single colony was inoculated into a 100 mL potato dextrose broth (PDB) (in 500 mL Erlenmeyer flasks with continuous shaking for ten days at 28 ◦C) and the PDA plates (15 mL agar media inverted incubated for five days at 28 ◦C) were treated with different concentrations (0, 10, 50, and 100 μM) of the DNMT inhibitor 5-aza and the HDAC inhibitor sodium butyrate, or a combination of the two, while the control cultures were treated with vehicle only (filter-sterilized H2O). The quantity of biomass is an essential parameter in the determination of a suitable epigenetic modifier or its optimal addition. After filtering the PDB liquid medium, the mycelium precipitate was washed three times with distilled water and lyophilized to constant weight as dry biomass. For the fungi that grow on PDA, the direct measurement of fungal biomass is hampered because the fungi penetrate into and bind themselves tightly to the solid-substrate particles. The indirect method based on the nucleic acid contents was adopted according to Liu's method [58], with some modifications. The pure mycelium of 0.05, 0.1, 0.15, 0.2, 0.25, and 0.3 g was extracted by adding 25 mL of 5% trichloroacetic acid solution in a water bath at 80 ◦C for 25 min with constant stirring and then cooled in an ice bath at 8000 r/min, centrifuged at 4 ◦C for 15 min, and diluted 5 times. The OD value was measured at 260 nm with 1% trichloroacetic acid as the blank control. Finally, dry biomass was quantified based on a standard curve between the nucleic acid content and dry biomass ranging from 0.05 to 0.3 g with y = 4.3543x − 0.0158 (R<sup>2</sup> = 0.998). All the culture groups were prepared and measured in 3 replicates. The HPLC profiles of the EtOAc extracts of the fungi cultivated in the presence of different epigenetic agents were tested. The cultures were extracted three times with EtOAc (50 mL × 3 for each PDA plate, 250 mL × 3 for each PDB flask). The EtOAc-soluble materials were passed over organic membranes and then subjected to HPLC analysis under conditions mentioned in Section 3.1.
