Industrial Production of Shikonin and Berberine

Summary

We have established industrial production processes for shikonin and berberine, secondary plant metabolites that have commercial and pharmaceutical uses, and have been producing shikonin commercially since 1983. Enhanced production of target metabolites is essential in order to lower the high production costs involved in the commercial process. Basic ways to increase productivity, thereby lowering costs, are 1) acquisition of a highly productive cell line, and 2) establishment of culture conditions and procedures that ensure maximum productivity of the cell line.

We obtained a highly productive berberine-producing cell line of Coptis japonica by repeated cell aggregate selection, and a highly productive shikonin-producing Lithospermum erythrorhizon cell line by protoplast selection. Then a two-stage culture method was established and the optimal concentrations of the components of the medium used at each stage were determined for the production of shikonin. Our berberine yields also were enhanced by the development of a method in which Coptis cells are cultured continuously at a density five times that used ordinarily.