Biomedicine

Abstract

Introduction and Aim: Simvastatin, a cholesterol-lowering drug, was manufactured industrially utilizing a multi-step semi-synthetic approach using lovastatin, naturally derived from Aspergillus terreus. Biocatalytic techniques are also used as a viable alternative. We provide an inexpensive mycological method for the bioconversion of lovastatin to simvastatin with easy downstream exertion. Methodology: Overall, 35 fungi and 2 Actinomycetes sp. were tested for bioconversion by culturing them in potato dextrose broth with lovastatin (1mg/ml) for 7 days at 28°C with shaking (110 rpm). Analysis employing thin layers and high-pressure liquid chromatography revealed Rhizopus sp. and Aspergillus sp. as positive isolates. These isolates were cultured using different liquid media comprising lactose, Maida, corn steep, and nitrogen-limiting media, alongside a solid medium (wheat bran). Finally, the crude sample was purified using gradient elution column chromatography. Results: Lactose medium and wheat bran produced the largest yields of simvastatin in both isolates, Rhizopus sp. (260 mg/L) and Aspergillus sp. (200 mg/L). Other media, on the contrary, produced a low yield (40 mg/L; 20 mg/L) for both isolates. The crude extract was purified using a 70:30 (benzene: acetonitrile, v/v) mobile phase, resulting in a maximum yield of 2.6mg/G dry weight with a measured purity of 96%. Conclusion: Unlike existing technologies, the bioconversion technique based on soil fungus is cost-effective, allowing for easy downstream exertion with high yield. As a result, the current process gives researchers a new opportunity to obtain simvastatin effectively.