Enhanced production of lovastatin in a bubble column by Aspergillus terreus using a two‐stage feeding strategy

Abstract

AbstractA two‐stage feeding strategy is shown to improve the rate of production of lovastatin by Aspergillus terreus when compared with conventional batch fermentation. The feeding strategy consisted of an initial batch/fed‐batch phase and a semi‐continuous culture dilution phase with retention of pelleted biomass in a slurry bubble column reactor. The batch phase served only to build up the biomass for producing lovastatin, a secondary metabolite that inhibits its own synthesis in the producing microfungus. The semi‐continuous dilution phase provided nutrients to sustain the fungus, but prevented biomass growth by limiting the supply of essential nitrogen. (Synthesis of lovastatin does not require nitrogen.) The preferred pelleted growth morphology that favors lovastatin synthesis was readily obtained and maintained in the 20 L bubble column used. In contrast, a stirred tank fermentation had a substantially lower production of lovastatin because mechanical agitation damaged the fungal pellets. The two‐stage feeding method increased lovastatin production rate by more than 50% in comparison with the conventional batch operation. Rheological data for the fungal broth are presented. Copyright © 2007 Society of Chemical Industry