Production of lovastatin by Aspergillus terreus: effects of the C:N ratio and the principal nutrients on growth and metabolite production

Abstract

Production of lovastatin and microbial biomass by Aspergillus terreus ATCC 20542 were influenced by the type of the carbon source (lactose, glycerol, and fructose) and the nitrogen source (yeast extract, corn steep liquor, and soybean meal) used and the C:N mass ratio in the medium. Use of a slowly metabolized carbon source (lactose) in combination with either soybean meal or yeast extract under N-limited conditions gave the highest titers and specific productivity (∼0.1 mg g −1 h −1 ) of lovastatin. The maximum value of the lovastatin yield coefficient on biomass was ∼30 mg g −1 using the lactose/soybean meal and lactose/yeast extract media. The optimal initial C:N mass ratio for attaining high productivity of lovastatin was ∼40. The behavior of the fermentation was not affected by the method of inoculation (fungal spores or hyphae) used, but the use of spores gave a more consistent inoculum in the different runs.

PRODUCTION OF LOVASTATIN AND SULOCHRIN BY Aspergillus terreus USING SOLID STATE FERMENTATION

“…terreus is widely used lovastatin producer of the industrial importance [4], which is extensively excreted from fungal cells into the medium in the form of β-hydroxy acid-mevinolinicacid [5]. As a kind of secondary metabolite of fungi, lovastatin is an intracellular product and mostly accumulated in mycelia.…”

“…As a kind of secondary metabolite of fungi, lovastatin is an intracellular product and mostly accumulated in mycelia. Submerged fermentation processes for largescale lovastatin production have been developed using A. terreus [3,5,6]. In submerged fermentation, its yield is proportional to the amount of biomass, with the high cell density causing the increase of the fermentation broth viscosity and the difficulty in stirring and oxygen mass transfer; an alternative strategy to produce lovastatin is by solid state fermentation (SSF) [7].…”

Response surface methodology for optimization of production of lovastatin by solid state fermentation

“…terreus have been successfully implemented for large-scale production (10) and most of the literature deals with this species (5,7,17). However, Szakacs et al (20) explored the possibility of lovastatin production from SSF by screening various strains of Aspergillus species for production of lovastatin in SSF and submerged fermentation (SmF).…”

Impact of bioreactor scale on lovastatin biosynthesis by Aspergillus terreus ATCC 20542 in a batch culture

“…There are several reports concerning it, both in shake flasks and bioreactors, in which different media and process conditions were used. In the experiments performed in shake flasks a significant impact on the course of lovastatin biosynthesis had, first of all, type and concentration of carbon and nitrogen sources (Bizukojć and Ledakowicz, 2007a;Casas Lopez et al, 2003). In bioreactors it was also necessary to use optimal pH (Bizukojć and Ledakowicz, 2008;Lai et al, 2005), oxygen saturation of broth and aeration rate (Casas Lopez et al, 2005;Lai et al, 2005;Rodriguez Porcel et al, 2006).…”