Assessment of fed-batch, semicontinuous, and continuous epothilone D production processes
Scott A Frykman1, Hiroko Tsuruta, Peter J Licari
1Department of Process Science, Kosan Biosciences, Inc., 3825 Bay Center Place, Hayward, CA 94545, USA. frykman@kosan.com
Biotechnology Progress
|August 6, 2005
Summary
This study enhances epothilone D production using adsorber resins in bioreactors. Continuous and semicontinuous systems with resin retention significantly increase epothilone D titers by nearly threefold.
Area of Science:
- Biotechnology
- Natural Product Synthesis
- Microbial Fermentation
Background:
- Epothilone D is a potent antineoplastic natural product derived from myxobacteria.
- Previous work established a fed-batch epothilone D production process using adsorber resin for in situ product capture and stabilization.
- Adsorber resins prevent product degradation within the bioreactor.
Purpose of the Study:
- To develop continuous and semicontinuous culturing systems for enhanced epothilone D production.
- To leverage adsorber resin technology for improved product titers and process efficiency.
- To demonstrate the general applicability of product retention strategies using adsorber resins.
Main Methods:
- Incorporation of adsorber resin beads into bioreactor systems for epothilone D capture.
- Development of bead retention mechanisms for continuous and semicontinuous culture systems.
- Comparison of product titers against a baseline fed-batch system.
Main Results:
- Continuous and semicontinuous culturing systems with resin retention achieved nearly threefold higher epothilone D product titers compared to the baseline fed-batch system.
- Complete product retention within the bioreactor was achieved using bead retention mechanisms.
- The developed strategies proved effective in increasing epothilone D yield.
Conclusions:
- Continuous and semicontinuous culturing systems incorporating adsorber resins and retention mechanisms significantly enhance epothilone D production.
- Product retention strategies using adsorber resins are broadly applicable to microbial cultivation processes requiring product capture.
- This approach offers a robust method for increasing titers of valuable microbial products.
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