Characterization of product capture resin during microbial cultivations.
Various bioactive small molecules produced by microbial cultivation are degraded in the culture broth or may repress the formation of additional product. The inclusion of hydrophobic adsorber resin beads to capture these products in situ and remove them from the culture broth can reduce or prevent this degradation and repression. These product capture beads are often subjected to a dynamic and stressful microenvironment for a long cultivation time, affecting their physical structure and performance. Impact and collision forces can result in the fracturing of these beads into smaller pieces, which are difficult to recover at the end of a cultivation run. Various contaminating compounds may also bind in a non-specific manner to these beads, reducing the binding capacity of the resin for the product of interest (fouling). This study characterizes resin bead binding capacity (to monitor bead fouling), and resin bead volume distributions (to monitor bead fracture) for an XAD-16 adsorber resin used to capture epothilone produced during myxobacterial cultivations. Resin fouling was found to reduce the product binding capacity of the adsorber resin by 25-50%. Additionally, the degree of resin bead fracture was found to be dependent on the cultivation length and the impeller rotation rate. Microbial cultivations and harvesting processes should be designed in such a way to minimize bead fragmentation and fouling during cultivation to maximize the amount of resin and associated product harvested at the end of a run.
Frykman
Scott
S
Department of Process Science, Kosan Biosciences Inc., 3832 Bay Center Place, Hayward, CA 94545, USA. frykman@kosan.com
Tsuruta
Hiroko
H
Galazzo
Jorge
J
Licari
Peter
P
D000327:Adsorption; D003505:Cyclodextrins / Q000737:chemistry; D034261:Epothilones / Q000096:biosynthesis / Q000737:chemistry*; D007218:Industrial Microbiology / Q000379:methods*; D008863:Microspheres; D009231:Myxococcales / Q000254:growth & development / Q000378:metabolism*; D010316:Particle Size; D012117:Resins, Synthetic / Q000737:chemistry*
D003505:Cyclodextrins; D034261:Epothilones; D012117:Resins, Synthetic