Improved Lovastatin Production via Targeted Medium Supplementation in Aspergillus terreus

Lovastatin is a clinically crucial cholesterol-lowering agent produced by Aspergillus terreus; however, its commercial biosynthesis remains limited due to suboptimal fermentation conditions. This study addresses the challenge of evaluating how the supplementation of l-cysteine (l-Cys), linoleic acid (LA), and riboflavin (vitamin B2) individually, in dual combinations, and, as a triple formulation, affects both fungal biomass and lovastatin yield. Among individual supplements, LA had the most pronounced effect, increasing lovastatin production to 1892.43 mg/L, whereas l-Cys and B2 yielded 1600.66 and 1176.82 mg/L, respectively. Dual combinations, such as l-Cys + LA and LA + B2, produced higher titers (2300 and 2282.96 mg/L, respectively), leading to significant increases in yield per gram of biomass. The highest productivity was achieved with triple supplementation (115 mg/L l-Cys + 90 mg/L LA + 0.66 mg/L B2), resulting in 2373.99 mg/L lovastatin, a biomass of 8.03 g/L, and a yield of 295.65 mg/g biomass. Biomass measurements across all treatments indicated that although fungal growth was moderately enhanced, the increase in lovastatin production was disproportionately greater. This suggests that the supplements primarily stimulate metabolic flux toward polyketide synthesis. These findings provide a foundation for media optimization strategies to enhance industrial-scale lovastatin production through precise nutrient control.