Lovastatin production by Aspergillus terreus in membrane gradostat bioreactor with two-stage feeding strategy

Lovastatin is a blood cholesterol-lowering agent and is produced as a secondary metabolite by Aspergillus terreus. Microbial production of this drug is carried out in solid-state or submerged culture, and due to difficulties of controlling the procedure parameters in solid-state method, the submerged method is conventional for industrial production. Although the submerged method is widely used, but this method damages the morphology of fungus due to shear stress caused by stirring. Since the morphology of fungus is a key factor in lovastatin production, using a bioreactor that causes the least damage to it, can improve the lovastatin production. In this paper, for the first time, it has been shown that the membrane gradostat bioreactor is suitable for lovastatin production, using A. terreus, due to providing suitable environmental conditions, therefore, it can be implemented as an alternative method for lovastatin production. Furthermore, it was found that implementing two-stage feeding, using different ratios of Carbon to Nitrogen in the culture medium, makes the lovastatin production to be 5 times more than one-stage feeding. Finally, it is shown that adding Zinc and Magnesium at the second stage further increases lovastatin production by 18%.