Enhanced Production of Epothilone by Immobilized Sorangium cellulosum in Porous Ceramics

Abstract

Epothilone, which is produced by the myxobacterium Sorangium cellulosum, contributes significant value in medicinal development. However, under submerged culture conditions, S. cellulosum will accumulate to form bacterial clumps, which hinder nutrient and metabolite transportation. Therefore, the production of epothilone by liquid fermentation is limited. In this study, diatomite-based porous ceramics were made from diatomite, paraffin, and poremaking agent (saw dust). Appropriate methods to modify the porous ceramics were also identified. After optimizing the preparation and modification conditions, we determined the optimal prescription to prepare high-performance porous ceramics. The structure of porous ceramics can provide a solid surface area where S. cellulosum can grow and metabolize to prevent the formation of bacterial clumps. S. cellulosum cells that do not form clumps will change their erratic metabolic behavior under submerged culture conditions. As a result, the unstable production of epothilone by this strain can be changed in the fermentation process, and the purpose of increasing epothilone production can be achieved. After 8 days of fermentation under optimized conditions, the epothilone yield reached 90.2 mg/l, which was increased four times compared with the fermentation without porous ceramics.

Keywords: Epothilone; Sorangium cellulosum; fermentation condition; immobilization; porous ceramic.