Optimizing production of asperolide A, a potential anti-tumor tetranorditerpenoid originally produced by the algal-derived endophytic fungus Aspergillus wentii EN-48

摘要

The marine algal-derived endophytic fungus Aspergillus wentii EN-48 produces the potential anti-tumor agent asperolide A,a tetranorlabdane diterpenoid active against lung cancer.However,the fermentation yield of asperolide A was very low and only produced in static cultures.Static fermentation conditions of A.wentii EN-48 were optimized employing response surface methodology to enhance the production of asperolide A.The optimized conditions resulted in a 13.9-fold yield enhancement,which matched the predicted value,and the optimized conditions were successfully used in scale-up fermentation for the production of asperolide A.Exogenous addition of plant hormones (especially 10 μmol/L methyl jasmonate) stimulated asperolide A production.To our knowledge,this is first optimized production of an asperolide by a marine-derived fungus.The optimization is effective and valuable to supply material for further anti-tumor mechanism studies and preclinical evaluation of asperolide A and other norditerpenoids.