Lovastatin production by Aspergillus terreus in a two-staged feeding operation

BACKGROUND: Lovastatin is known to inhibit its own synthesis in the fungus Aspergillus terreus. Therefore, the use of a fermentation strategy that continuously removes some of the lovastatin produced from the bioreactor can enhance its productivity. This paper reports on the effects of dilution rate and the composition of the feed medium on lovastatin production by A. terreus. RESULTS: The feeding strategy consisted of an initial batch/fed-batch phase and a semi-continuous culture phase in which the pelleted biomass was retained inside a slurry bubble column. A nitrogen-free medium was fed at various fixed dilution rates in the semi-continuous phase. In experiments that were designed to assess the effects of the composition of the medium, the dilution rate was held at 0.42 d−1, but different feed media were used in separate runs. The best two-staged production strategy was shown to consist of a 96 h batch/fed-batch phase that used a nutritionally complete medium. This was followed by a semi-continuous operation using a medium that was free of both nitrogen and carbon sources. CONCLUSION: Semi-continuous operation enhanced productivity of lovastatin by 315% compared with a conventional batch operation. The optimal dilution rate in semi-continuous operation was about 0.42 d−1.  2008 Society of Chemical Industry