Transferability of bioprocessing modes for recombinant protease production: from fed-batch to continuous cultivation with Bacillus licheniformis

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Publié dans:BMC Biotechnology vol. 25 (2025), p. 1
Auteur principal: Kittler, Stefan
Autres auteurs: Müller, Fabian, Elshazly, Mohamed, Wandrey, Georg Benjamin, Klein, Tobias, Daub, Andreas, Spadiut, Oliver, Kopp, Julian
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Springer Nature B.V.
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022 |a 1472-6750 
024 7 |a 10.1186/s12896-025-00947-9  |2 doi 
035 |a 3165418130 
045 2 |b d20250101  |b d20251231 
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100 1 |a Kittler, Stefan 
245 1 |a Transferability of bioprocessing modes for recombinant protease production: from fed-batch to continuous cultivation with <i>Bacillus licheniformis</i> 
260 |b Springer Nature B.V.  |c 2025 
513 |a Journal Article 
520 3 |a BackgroundProteases are essential in various industries due to their unique substrate specificities and robustness in different operational conditions. Bacillus strains consist of a genotype favorable for rapid growth whilst secreting enzymes extracellularly, thereby simplifying recombinant protease production. Despite the widespread use of batch and fed-batch fermentations for their ease and robustness, these cultivation types are often marred by significant energy requirements and prolonged downtimes. The switch towards continuous cultivation methods promises reduced carbon footprints and improved equipment efficiency. Yet, research focusing on Bacillus strains is limited, therefore we aimed to establish a continuous cultivation as a competitive alternative to fed-batch.ResultsTherefore, this study aimed to explore the potential of chemostat cultivations for producing a protease from Bacillus licheniformis utilizing a derepressed induction system, and comparing specific productivities and space-time yields to fed-batch cultivations. The continuous cultivations were described in a hybrid model, considering the effect of productivity as function of the applied dilution rate as well as the generation time. The workflow of this study demonstrates that screenings in a fed-batch mode and chemostat cultivations conducted at the same growth rate, result in different specific productivities for derepressible systems.ConclusionThe results of this study highlight that the feeding rate’s impact on specific productivity varies significantly between fed-batch and chemostat cultivations. These differences suggest that fed-batch screenings may not be adequate for developing a continuous process using a derepressed promoter system in B. licheniformis. Although the space-time yield of fed-batch cultivations has not been surpassed by stable continuous operations—achieving only a third of the highest space-time yield observed in fed-batch—valuable mechanistic insights have been gained. This knowledge could facilitate the transition towards a more sustainable mode of cultivation for industrial protease production. 
610 4 |a BASF SE 
651 4 |a Switzerland 
651 4 |a Germany 
653 |a Physiology 
653 |a Bioprocessing 
653 |a Workflow 
653 |a Productivity 
653 |a Fed batch 
653 |a Batch culture 
653 |a Metabolism 
653 |a Batch processing 
653 |a Feeding rates 
653 |a Genotypes 
653 |a Industrial production 
653 |a Energy consumption 
653 |a Robustness 
653 |a Proteins 
653 |a Fermentation 
653 |a Energy requirements 
653 |a Continuity (mathematics) 
653 |a Protease 
653 |a Dilution 
653 |a Sensors 
653 |a Batch processes 
653 |a Process controls 
653 |a Bioreactors 
653 |a Enzymes 
653 |a Strains (organisms) 
653 |a Cultivation 
653 |a Carbon footprint 
653 |a Proteinase 
653 |a Bacillus licheniformis 
653 |a Economic 
653 |a Bacillus 
653 |a Environmental 
700 1 |a Müller, Fabian 
700 1 |a Elshazly, Mohamed 
700 1 |a Wandrey, Georg Benjamin 
700 1 |a Klein, Tobias 
700 1 |a Daub, Andreas 
700 1 |a Spadiut, Oliver 
700 1 |a Kopp, Julian 
773 0 |t BMC Biotechnology  |g vol. 25 (2025), p. 1 
786 0 |d ProQuest  |t Health & Medical Collection 
856 4 1 |3 Citation/Abstract  |u https://www.proquest.com/docview/3165418130/abstract/embedded/L8HZQI7Z43R0LA5T?source=fedsrch 
856 4 0 |3 Full Text  |u https://www.proquest.com/docview/3165418130/fulltext/embedded/L8HZQI7Z43R0LA5T?source=fedsrch 
856 4 0 |3 Full Text - PDF  |u https://www.proquest.com/docview/3165418130/fulltextPDF/embedded/L8HZQI7Z43R0LA5T?source=fedsrch