Fermentation optimization for the production of lovastatin by Aspergillus terreus: use of response surface methodology

A Box–Behnken experimental design was used to investigate the effects of five factors—ie oxygen content in the gas phase; concentrations of C, N and P; and fermentation time—on the concentrations of biomass and lovastatin produced in batch cultures of Aspergillus terreus. The values of the various factors in the experiment ranged widely, as follows: 20–80% (v/v) oxygen in the aeration gas; 8–48 g dm−3 C-concentration; 0.2–0.6 g dm−3 N-concentration; 0.5–2.5 g dm−3 phosphate-concentration; and 7–11 days fermentation time. No previous work has used statistical analysis in documenting the interactions between oxygen supply and nutrient concentrations in lovastatin production. The Box–Behnken design identified the oxygen content in the gas phase as the principal factor influencing the production of lovastatin. Both a limitation and excess of oxygen reduced lovastatin titers. A medium containing 48 g dm−3 C supplied as lactose, 0.46 g dm−3 N supplied as soybean meal, and 0.79 g dm−3 phosphate supplied as KH2PO4, was shown to support high titers (∼230 mg dm−3) of lovastatin in a 7-day fermentation in oxygen-rich conditions (80% v/v oxygen in the aeration gas). Under these conditions, the culture medium had excess carbon but limiting amounts of nitrogen. The optimized fermentation conditions raised the lovastatin titer by four-fold compared with the worst-case scenario within the range of factors investigated.  2004 Society of Chemical Industry