Enhanced l-Methioninase production by Methylobacterium sp. JUBTK33 through RSM and its anticancer potential

Abstract

l-Methioninase (E.C.4.4.1.11) has gained greater significance due to its anticancer potential. In the present study, high l-Methioninase activity was seen in a newly isolated bacterium, Methylobacterium sp. JUBTK33. Enhancing enzyme production and activity is crucial for exploring the strain towards industrial applications. Hence, optimization of media components was carried out using one factor at a time method followed by statistical approach of Response Surface Methodology (RSM)– CCD matrix using Design-Expert software. After conducting triplicates of all thirty runs, Glucose 1%, Yeast 1%, and media of pH 7.0, and Tapioca peel at 10%, were found to be the optimal parameters for enhancing enzyme production from 1.26 U/mL/min to 2.10 U/mL/min (1.7 folds). The regression model analysis R2 value 95.8% indicated the best fitness model in explaining relationship between the responses and the variables. Further, the enzyme produced from the bacteria was analyzed for its cytotoxicity to Breast cancer (MCF-7), Hepatocellular carcinoma (Hep-G2), cervical cancer (HeLa), and Human embryonic Kidney (HEK-293) cell lines, with Doxorubicin as the positive control. This enzyme was effective on the Breast cancer cell line with 11% cell viability at 400 μg/mL, while Doxorubicin showed 4% viability. Toxicity of the enzyme on healthy cells seen as 44%, whereas Doxorubicin showed 83%. The study demonstrates the suitability of statistical methods in enhancing the enzyme productivity and promising anticancer activity of the l-Methioninase from Methylobacterium sp., with lesser toxicity towards healthy cells. l-Methioninase from the newly isolated Methylobacterium sp. has promising characteristics towards anticancer drug developmental studies.