Bioconversion of Alternative Substrates for the Biosynthesis of HMG-CoA Reductase Inhibitors by Aspergillus spp. Strains with Antimicrobial Potential

Simvastatin, a semisynthetic drug widely used to lower cholesterol, is among the most prescribed statins worldwide. This study focuses on the direct production of a simvastatin-like biomolecule using alternative substrates by Aspergillus spp. strains. Two species, A. terreus UCP 1276 and A. flavus UCP 0316, were initially evaluated in synthetic media as control. Subsequently, the carbon and nitrogen sources were replaced by agro-industrial substrates, resulting in five modified media. Cultures were maintained at 28 °C, pH 6.5, at 180 rpm for 21 days. Fungal growth kinetics were evaluated and a 23 full-factorial design (FFD) was used to investigate the influence of substrate concentration on statin yield. Presence of inhibitors was confirmed by bioassay, UV–visible spectrophotometry, and thin-layer chromatography (TLC). According to the results, A. flavus UCP yielded 0.24 mg/g of statin in condition 2 of FFD (medium containing 4.5% soluble starch and saline base), suggesting it as a promising candidate for direct production of the biomolecule. Statistical analysis showed the significant effect of soluble starch on inhibitor production, making it a viable and profitable alternative substrate. Moreover, the isolated statin exhibited broad-spectrum antimicrobial activity, including efficacy against Gram-negative and Gram-positive bacteria and yeasts, indicating therapeutic potential against antimicrobial resistance.