Dual aerobic hollow-fiber bioreactor for cultivation ofStreptomyces aureofaciens

Abstract

Streptomyces aureofaciens (ATCC 12416c) was grown in the interstitial region formed by a parallel arrangement of three hollow silicone tubules contained within a microporous polypropylene hollow fiber. Liquid-soluble nutrients were supplied by diffusion across the polypropylene fiber to the interstitial cell-containing region whereas air or oxygen was provided by diffusion from the silicone tubule lumina to the cell mass. In this bioreactor, S. aureofaciens grew to high cell densities (greater than 10¹¹ cells/cm³) and the culture so-obtained continously synthesized the secondary metabolite tetracycline. The volumetric productivity of tetracycline based on the interstitial volume was 90 μg/ml/h and based on the total reactor volume was 5.5 μg/mL/h. The high surface area-to-volume ratio afforded by the cylindrical configuration together with spatially distinct conduits to continuously transport liquids and gases, each of which may be nutrients or products of biosynthesis, to or from a tissuelike cell mass provides an alternative to the conventional air- or oxygen-sparged fermentation vessel. High volumetric reactor productivities may be achieved by virute of the concentrated stationary cell mass and by the appropriate selection of fiber sizes and materials so as to ensure adequate supplies of liquid and gaseous substrates to, as well as removal of metabolites from, most cells in the culture. This reactor topology is quite general and may be adapted to most microbial as well as mammalian and plant cell systems.