Novel approaches to improve lovastatin production in membrane gradostat bioreactor

Abstract

Lovastatin is a blood cholesterol reduction medicine and can be produced as a fungal secondary metabolite. Although the industrial production of lovastatin is generally achieved by Aspergillus terreus fungus in submerged culture, it was previously found that a membrane gradostat bioreactor (MGB) is more suitable than a stirred tank due to the absence of shear stress. However, a major challenge in these bioreactors is that oxygen penetration reduces as the biofilm thickness increases, which depreciates lovastatin production. To overcome this problem, two novel approaches are proposed for cultivating A. terreus in MGB. It was found that using monosodium glutamate (MSG) as a nitrogen source prevents biofilm growth and improves lovastatin production as a secondary metabolite. Therefore, implementing a two-stage feeding is proposed. In this strategy, the first four days were dedicated to biofilm growth to achieve a desirable biofilm thickness, and yeast extract was used as a nitrogen source. The next six days were dedicated to lovastatin production and the nitrogen source was changed to MSG to prevent biofilm growth and improve lovastatin production. Implementing this strategy, lovastatin production was approximately 6.5 times higher than the maximum lovastatin production using only yeast extract as the nitrogen source. Moreover, the effect of magnesium silicate (talc) microparticles was examined, and results showed an improvement in oxygen penetration to the inner layers of the biofilm. Thus, using talc in the inoculation stage is proposed. In this approach without changing the nitrogen source, lovastatin production increased by 48% Compared to the control run.