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(-1) 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 (similar to230 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. (C) 2004 Society of Chemical Industry.