Novelty in elicitation of simvastatin production from Aspergillus terreus AJ73 and evaluation of immobilized simvastatin on carbon nanotube as anticancer activity

Simvastatin is a cholesterol-lowering drug widely employed to control cholesterol levels and to prevent stroke and cardiac failure in patients at a high risk of coronary artery disease. Furthermore, Simvastatin has a role as an antimicrobial and anti-cancer agent. The continual increase in productivity that occurs by strain enhancement is crucial for a commercial fermentation process's viability. Elicitation by other microorganisms is a crucial example of these improvements. Three microorganisms strains (live and dead) were utilized for elicitation of local isolate Aspergillusterreus AJ73 to enhance the production of simvastatin utilizing solid-state fermentation. These microorganism strains are Trichoderma viridae, Saccharomyses cerevisiae, and Bacillus subtilus. Three various inoculum sizes of the elicitors (0.25, 0.5, and 1 ml/5gm of 1x10⁶ cells or spores/ml) were employed and incubated at 28 ºC for 6 days (pH 7.0). Elicitors were spent medium with dead cells, spent medium with live cells, live cells, dead cells, and spent medium without live cells or dead cells. The results demonstrated that the maximum production of simvastatin was 260 µg/gm-substrate in the culture elicited with 1 ml/5gm (1x10⁶ cells/ml) of live S.cerevisiae without spent medium compared with the control culture (Aspergillus terreus AJ73 culture without any addition) (91.31 µg/gm). While elicitation by some other elicitors showed a low concentration of simvastatin synthesis by A.terreus AJ73 utilizing SSF (fluidized bed, consisting wheat bran and oat bran (1:1 w:w), the moisture ratio was (1.2 v:w) by sodium acetate (0.01 M), pH 7.0). The results of cytotoxic activity of free and immobilized simvastatin on carbon nanotubes (MWCNTs)  revealed a decrease to a depress in cell viability in a dose-dependent manner on HL-60 cell lines, with a calculating IC₅₀ of 133.65 and 73.43 µg/ml, respectively, compare with normal cell line (HdFn cell line) at IC₅₀ of 188.34 and 163.17 µg/ml, respectively.