“…Many authors have reported that the limitations of the classical optimization approach can be overcome by using statistics-based methods such as response surface methodology (RSM). RSM is a combined statistical method used for searching the optimum conditions and designing experiments, developing models and assessing the effects of factors (Choudhari and Singhal, 2008; Kalil et al , 2000; Yan et al , 2013), and it has been extensively used in the optimization of media for the production of microbial metabolites by various researchers (Choudhari and Singhal, 2008; Goksungur et al , 2002; Kalil et al , 2000; Nanou and Roukas, 2011; Yan et al , 2013).…”