Abstract: Culture media and fermentation conditions for cultivation of Penicillium sp. S-1-16 isolated from an Antarctic sea cucumber sample were investigated to improve the yield of secondary metabolites with modest cytotoxic activity against three cancer cell lines. The optimum fermentation conditions, including medium, temperature, and type of water, were identified based on fungal biomass, secondary metabolite production, and antitumor activity. The initial fermentation conditions were as follows: 0.3% yeast powder, 0.5% peptone, 0.3% maltose, 1% glucose, 5% sucrose, tap water, a 15% inoculum size, an initial pH of 7.0, and incubation at 18°C, with shaking at 180 r·m^-1, for 15 d. Under the optimized fermentation conditions , the amount of secondary metabolites and their cytotoxic activity increased by 568.75% and 265%, respectively, compared with the initial conditions. Additionally, the secondary metabolites’ inhibition of the growth of HeLa and SGC-7901 cells increased from 0 to 48.19% and 69.18%, respectively, after the optimization. These results provide clues for subsequent separation and purification of secondary metabolites derived from the Penicillium sp. S-1-16 strain.

Key words: Antarctica fungus, Penicillium sp. S-1-16, Cytotoxic activity, Pre-optimization