Understanding Process Variables and their Interactions for Maximizing Production of Artemisinin Derivative Artemether (Anti-Malarial Drug) Through Cunninghamella echinulata var elegans at 5 L Bioreactor Level

Abstract

Background: Malaria is one of the life threatening diseases which is caused by Plasmodium sp. of protozoa and uses Anopheles mosquitos as vector. Plasmodium vivax and Plasmodium falciparum are common form of malaria parasite. Artemisinin is reported for its antimalarial activities and Artemether which is a methyl ether derivative of Artemisinin, has been found effective against P. falciparum. Methods: In the present study, bioconversion of Artemisinin into Artemether was carried out experimentally and the statistical tools like experimental factorial design and Response Surface Methodology were used to find optimal conditions (concentration of Artemisinin, age of inoculum, temperature & pH) using Cunninghamella echinulata var. elegans. Experimental conditions for maximum product recovery from culture broth were also optimized using various polar and non-polar solvents for extraction. Artemether purity was analyzed by reverse-phase HPLC. Experimental data was fitted in a quadratic model and effect of various parameters was analyzed. Results: It was found that bioconversion of Artemisinin into Artemether is growth associated process. It was observed that molasses used as carbon source supported production of Artemether to 3.4g/L. The biomass and oxygen are key element affecting of bioconversion of Artemisinin into Artemether such as higher dissolved oxygen reduced the Artemether bioconversion. The highest bioconversion of Artemisinin into Artemether was obtained at temperature 25.5oC, 5g/L concentration of Artemisinin, at age of inoculum of 44.5 h and at pH 6.0. Model suggested the highest bioconversion of Artemisinin into Artemether was 54% at shake flask level which was near about experimental finding. An optimal condition for bioconversion was also analyzed and 64% bioconversion was obtained in 5L bioreactor. Conclusion: The outcomes of the study provided optimum conditions for bioconversion of Artemisinin into Artemether.