Characterization of an Endophytic Fusarium odoratissimum Strain 25^# from Dysosma versipellis with Putative...

Podophyllotoxin has significant anti-tumour, anti-condyloma and anti-HIV characteristics, and its derivatives, such as etoposide (VP 16-213), teniposide (VM-26) and Etopophos, have been approved in the market by the US FDA and are widely used in the clinical treatment of various cancers, such as lymphoma, lung cancer and acute leukaemia. Podophyllotoxin is currently extracted primarily from certain species of the Podophyllum genus (e.g., P. hexandrum and P. peltatum), while excessive harvesting of these wild resources has led to their progressive depletion. Podophyllotoxin can be obtained by chemical synthesis, semi-synthesis or tissue culture, but the high production cost, low yield and environmental pollution greatly limit its large-scale production and application. In this study, an endophytic fungus 25^# putatively producing podophyllotoxin was obtained from the rhizomes of an endangered medicinal plant Dysosma versipellis. Based on multi-gene phylogenetic analyses (including tef1, tub2, rpb2, and cmdA sequence data) and morphological characteristics, the strain was identified as Fusarium odoratissimum. By using HPLC and UPLC-QTOF-MS/MS, the isolate was found to produce a compound putatively identified as podophyllotoxin, with an estimated yield of 269.0 µg·g^- 1 (dry mycelial weight). Biological evaluation revealed that the mycelial methanolic extract possessed antibacterial activity against Staphylococcus aureus, Escherichia coli, and Micrococcus luteus, with inhibition zones of 13.1, 16.3, and 17.1 mm, respectively. Furthermore, the mycelial ethyl acetate extract exhibited measurable cytotoxic activity against the HepG2 cell line (IC₅₀ = 32.58 ± 1.61 µg·mL^- 1). Quantitative correlation analysis suggested that the estimated PTOX-equivalent concentration in the crude extract was in reasonable agreement with the IC₅₀ of the pure PTOX standard, indicating that F. odoratissimum 25^# may represent a potential natural source of a compound putatively identified as podophyllotoxin.