A genetic algorithm has been used to optimize the composition of the culture medium for growing the microalga Nannochloropsis gaditana, based on the nutrients composition of the commercial medium ALGAL. This strategy was carried out through the implementation of 270 experiments spread over nine generations, which allowed achieving an eicosapentaenoic acid (EPA) productivity of 17.8 mg L-1 d(-1) in a continuous culture of N. gaditana, with an increase of 23% compared to the commercial medium. The EPA yield on nitrogen and phosphorous, 0.042 and 1.146 gEPA gs(-1), respectively, were 40% and 5-fold higher, respectively, than the values obtained with the nitrogen-optimized ALGAL medium. This improvement was obtained with the medium G-8, which also allowed reducing the requirement of several nutrients such as P, Mo, Mn in 74%, 69% and 66%, respectively, as well as the thiamine content a 46%. (C) 2014 Elsevier Ltd. All rights reserved.