Repetitive Fed-Batch: A Promising Process Mode for Biomanufacturing With E. coli
Recombinant protein production with Escherichia coli is usually carried out in fed-batch mode in industry. As set-up and cleaning of equipment are time- and cost-intensive, it would be economically and environmentally favorable to reduce the number of these procedures. Switching from fed-batch to co...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2020.573607/full |
| _version_ | 1818116154344865792 |
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| author | Julian Kopp Stefan Kittler Christoph Slouka Christoph Herwig Oliver Spadiut David J. Wurm |
| author_facet | Julian Kopp Stefan Kittler Christoph Slouka Christoph Herwig Oliver Spadiut David J. Wurm |
| author_sort | Julian Kopp |
| collection | DOAJ |
| description | Recombinant protein production with Escherichia coli is usually carried out in fed-batch mode in industry. As set-up and cleaning of equipment are time- and cost-intensive, it would be economically and environmentally favorable to reduce the number of these procedures. Switching from fed-batch to continuous biomanufacturing with microbials is not yet applied as these cultivations still suffer from time-dependent variations in productivity. Repetitive fed-batch process technology facilitates critical equipment usage, reduces the environmental fingerprint and potentially increases the overall space-time yield. Surprisingly, studies on repetitive fed-batch processes for recombinant protein production can be found for yeasts only. Knowledge on repetitive fed-batch cultivation technology for recombinant protein production in E. coli is not available until now. In this study, a mixed feed approach, enabling repetitive fed-batch technology for recombinant protein production in E. coli, was developed. Effects of the cultivation mode on the space-time yield for a single-cycle fed-batch, a two-cycle repetitive fed-batch, a three-cycle repetitive fed batch and a chemostat cultivation were investigated. For that purpose, we used two different E. coli strains, expressing a model protein in the cytoplasm or in the periplasm, respectively. Our results demonstrate that a repetitive fed-batch for E. coli leads to a higher space-time yield compared to a single-cycle fed-batch and can potentially outperform continuous biomanufacturing. For the first time, we were able to show that repetitive fed-batch technology is highly suitable for recombinant protein production in E. coli using our mixed feeding approach, as it potentially (i) improves product throughput by using critical equipment to its full capacity and (ii) allows implementation of a more economic process by reducing cleaning and set-up times. |
| first_indexed | 2024-12-11T04:18:00Z |
| format | Article |
| id | doaj.art-cb141ed4f8e24e8e882c747741f62b93 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-12-11T04:18:00Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-cb141ed4f8e24e8e882c747741f62b932022-12-22T01:21:12ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852020-11-01810.3389/fbioe.2020.573607573607Repetitive Fed-Batch: A Promising Process Mode for Biomanufacturing With E. coliJulian KoppStefan KittlerChristoph SloukaChristoph HerwigOliver SpadiutDavid J. WurmRecombinant protein production with Escherichia coli is usually carried out in fed-batch mode in industry. As set-up and cleaning of equipment are time- and cost-intensive, it would be economically and environmentally favorable to reduce the number of these procedures. Switching from fed-batch to continuous biomanufacturing with microbials is not yet applied as these cultivations still suffer from time-dependent variations in productivity. Repetitive fed-batch process technology facilitates critical equipment usage, reduces the environmental fingerprint and potentially increases the overall space-time yield. Surprisingly, studies on repetitive fed-batch processes for recombinant protein production can be found for yeasts only. Knowledge on repetitive fed-batch cultivation technology for recombinant protein production in E. coli is not available until now. In this study, a mixed feed approach, enabling repetitive fed-batch technology for recombinant protein production in E. coli, was developed. Effects of the cultivation mode on the space-time yield for a single-cycle fed-batch, a two-cycle repetitive fed-batch, a three-cycle repetitive fed batch and a chemostat cultivation were investigated. For that purpose, we used two different E. coli strains, expressing a model protein in the cytoplasm or in the periplasm, respectively. Our results demonstrate that a repetitive fed-batch for E. coli leads to a higher space-time yield compared to a single-cycle fed-batch and can potentially outperform continuous biomanufacturing. For the first time, we were able to show that repetitive fed-batch technology is highly suitable for recombinant protein production in E. coli using our mixed feeding approach, as it potentially (i) improves product throughput by using critical equipment to its full capacity and (ii) allows implementation of a more economic process by reducing cleaning and set-up times.https://www.frontiersin.org/articles/10.3389/fbioe.2020.573607/fullE. colirepetitive fed-batchprocess understandingprocess intensificationrecombinant protein productioncontinuous biomanufacturing |
| spellingShingle | Julian Kopp Stefan Kittler Christoph Slouka Christoph Herwig Oliver Spadiut David J. Wurm Repetitive Fed-Batch: A Promising Process Mode for Biomanufacturing With E. coli Frontiers in Bioengineering and Biotechnology E. coli repetitive fed-batch process understanding process intensification recombinant protein production continuous biomanufacturing |
| title | Repetitive Fed-Batch: A Promising Process Mode for Biomanufacturing With E. coli |
| title_full | Repetitive Fed-Batch: A Promising Process Mode for Biomanufacturing With E. coli |
| title_fullStr | Repetitive Fed-Batch: A Promising Process Mode for Biomanufacturing With E. coli |
| title_full_unstemmed | Repetitive Fed-Batch: A Promising Process Mode for Biomanufacturing With E. coli |
| title_short | Repetitive Fed-Batch: A Promising Process Mode for Biomanufacturing With E. coli |
| title_sort | repetitive fed batch a promising process mode for biomanufacturing with e coli |
| topic | E. coli repetitive fed-batch process understanding process intensification recombinant protein production continuous biomanufacturing |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2020.573607/full |
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