Paraherquamide A(PA) is an important raw material for the new anthelmintic drug Startect^®,and its low yield limits the promotion and use of the drug.Response surface methodology (RSM) was used to optimize the fermentation process of wild Penicillium sp.KWF31 to produce PA.Eight factors of the medium were screened by Plackett-Burman test design.Among them,the dosages of soluble starch,glucose and yeast extract were found to be the key factors.The optimal concentration ranges of the three factors were examined by the steepest ascent path and the Box-Behnken design as 31.0 g/L soluble starch,12.8 g/L glucose and 14.5 g/L yeast extract,respectively.Under the optimal condition,the maximum titer of PA approached 243.7 mg/L,which was close to the theoretical value of 241.6 mg/L,and 3.4 times of the initial.