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Bioengineering
Special Issues
Strategies for the Efficient Development of Microbial Bioprocesses
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Strategies for the Efficient Development of Microbial Bioprocesses

A special issue of Bioengineering (ISSN 2306-5354). This special issue belongs to the section "Biochemical Engineering".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 10265

Special Issue Editors

Prof. Dr. Peter Neubauer

E-Mail Website
Guest Editor
Department of Bioprocess Engineering, Technische Universität Berlin, Ackerstraβe 76, ACK24, D-13355 Berlin, Germany
Interests: bioprocess development; Escherichia coli physiology; recombinant proteins; cocultivation; fed-batch; continuous culture
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Christoph Herwig

E-Mail Website
Guest Editor
Lisalis GmbH, Jenbachgasse 73-2, 1130 Vienna, Austria
Interests: biopharmaceutical process development
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The consistent development of new bioprocesses needs to be performed at the perspective of the final process scale. Therefore, an efficient bioprocess development should consider large‑scale effects and integrate them from early stages onwards together with process analytical technologies (PAT) and quality by design (QbD). This includes technical challenges (sensors, modelling), the cellular dynamic regulatory networks and population dynamics. Current progresses in automation and parallelization demand for a higher degree of digitalization and advanced data treatment. The aim of this Special Issue is to discuss the efficiency of the whole product and process life cycle, from the raw materials and early screening stages to industrial scale production and final application. This Special Issue is a joint project of the journals Microorganisms and Bioengineering and focuses on contributions at the 6th BioProScale Symposium and 7th BioProScale Symposium, which were organized as a digital event from 29–31 March 2021 and 28–31 March 2022, but further contributions are also invited on the following subjects:

Industrial-scale bioprocessing (scale-down and scale-up approaches, industrial-scale operation, population heterogeneity, process monitoring and advanced control, modelling of industrial-scale processes, mixing and reactor characterization, process robustness and repeatability, integrated upstream and downstream operations), process analytical technologies (PAT, multiparameter analysis, non-invasive sensors, single-cell based monitoring, soft sensors, fault identification and diagnosis, multiposition measurements, data handling and exploration, monitoring and control of co- and mixed cultures), high-throughput bioprocessing and automation (lab automation and robotics, automated screenings in bioprocess development, DoE, model‑based experimental designs, algorithm based operations and operational space characterisation, evolutionary strategies for strains and processes, communication trends for dynamic device operation and data flow, high-throughput strain engineering) and bioprocesses for a circular economy (waste streams to value-added products, pretreatment, feedstock flexibility, scale-up/scale-down of biorefinery concepts, closed carbon cycles, smart bioproduction grids, decentralised production).

The papers related to microbiology are welcome for Microorganisms, related to engineering and other fields are welcome for Bioengineering. The Joint Special Issue in Microorganisms: Strategies for the Efficient Development of Microbial Bioprocesses

Prof. Dr. Peter Neubauer
Prof. Dr. Christoph Herwig
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Bioengineering is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Prof. Dr. Peter Neubauer
Prof. Dr. Christoph Herwig
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Bioengineering is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (4 papers)

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Research

23 pages, 2987 KiB  
Article
Online 2D Fluorescence Monitoring in Microtiter Plates Allows Prediction of Cultivation Parameters and Considerable Reduction in Sampling Efforts for Parallel Cultivations of Hansenula polymorpha
by Christoph Berg, Nina Ihling, Maurice Finger, Olivier Paquet-Durand, Bernd Hitzmann and Jochen Büchs
Bioengineering 2022, 9(9), 438; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9090438 - 04 Sep 2022
Cited by 5 | Viewed by 2043
Abstract
Multi-wavelength (2D) fluorescence spectroscopy represents an important step towards exploiting the monitoring potential of microtiter plates (MTPs) during early-stage bioprocess development. In combination with multivariate data analysis (MVDA), important process information can be obtained, while repetitive, cost-intensive sample analytics can be reduced. This [...] Read more.
Multi-wavelength (2D) fluorescence spectroscopy represents an important step towards exploiting the monitoring potential of microtiter plates (MTPs) during early-stage bioprocess development. In combination with multivariate data analysis (MVDA), important process information can be obtained, while repetitive, cost-intensive sample analytics can be reduced. This study provides a comprehensive experimental dataset of online and offline measurements for batch cultures of Hansenula polymorpha. In the first step, principal component analysis (PCA) was used to assess spectral data quality. Secondly, partial least-squares (PLS) regression models were generated, based on spectral data of two cultivation conditions and offline samples for glycerol, cell dry weight, and pH value. Thereby, the time-wise resolution increased 12-fold compared to the offline sampling interval of 6 h. The PLS models were validated using offline samples of a shorter sampling interval. Very good model transferability was shown during the PLS model application to the spectral data of cultures with six varying initial cultivation conditions. For all the predicted variables, a relative root-mean-square error (RMSE) below 6% was obtained. Based on the findings, the initial experimental strategy was re-evaluated and a more practical approach with minimised sampling effort and elevated experimental throughput was proposed. In conclusion, the study underlines the high potential of multi-wavelength (2D) fluorescence spectroscopy and provides an evaluation workflow for PLS modelling in microtiter plates. Full article
(This article belongs to the Special Issue Strategies for the Efficient Development of Microbial Bioprocesses)
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14 pages, 1191 KiB  
Article
Diet Shift May Trigger LuxS/AI-2 Quorum Sensing in Rumen Bacteria
by Xiao Wei, Tanghui Long, Yanjiao Li, Kehui Ouyang and Qinghua Qiu
Bioengineering 2022, 9(8), 379; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9080379 - 10 Aug 2022
Cited by 2 | Viewed by 1892
Abstract
Recent studies have revealed that LuxS/AI-2 quorum sensing (QS) is the most universal cell-to-cell communication in rumen bacteria; however, it remains unknown how they respond to nutritional stress from a diet shift. This study aimed to explore whether a diet shift could trigger [...] Read more.
Recent studies have revealed that LuxS/AI-2 quorum sensing (QS) is the most universal cell-to-cell communication in rumen bacteria; however, it remains unknown how they respond to nutritional stress from a diet shift. This study aimed to explore whether a diet shift could trigger rumen bacterial LuxS/AI-2 QS and its influences on rumen fermentation characteristics and bacterial community diversity and composition. A total of fifteen Hu sheep were selected to undergo a pre-shift diet (Pre, concentrate to forage ratio 75:25) for one month and then abruptly switch to a post-shift diet (Post, concentrate to forage ratio 49:51). Results showed that the serum cortisol and immunoglobulin G concentrations were higher in Post than in Pre (p < 0.05). The microbial density, AI-2 concentration, biofilm formation, and the gene expression of ftsH were higher in Post when compared with Pre (p < 0.05), whilst the gene expression of luxS tended to be lower in Post (p = 0.054). The molar concentration of valerate and fermentation efficiency decreased after the diet shift, while the acetate to propionate ratio and the molar proportion of butyrate were higher in Post compared to Pre (p < 0.05). Moreover, the diet shift increased the richness of ruminal bacteria and the relative abundances of Roseburia, Prevotellaceae UCG-001, and Lachnospira, and decreased the relative abundances of Prevotella, Megasphaera, and Dialister (p < 0.05). A difference in trends was also observed in an analysis of similarity (R = 0.1208 and p = 0.064). This study suggests that a diet shift could trigger rumen bacterial LuxS/AI-2 QS by altering microbial density, AI-2 concentration, biofilm formation, and related gene expression, as well as affect the rumen fermentation pattern and bacterial community diversity and composition. This study may provide insight into a potential strategy for relieving nutritional stress via regulating bacterial communication. Full article
(This article belongs to the Special Issue Strategies for the Efficient Development of Microbial Bioprocesses)
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15 pages, 3919 KiB  
Article
Environmental Factors Modulate the Role of orf21 Sigma Factor in Clavulanic Acid Production in Streptomyces Clavuligerus ATCC27064
by Luisa F. Patiño, Vanessa Aguirre-Hoyos, Laura I. Pinilla, León F. Toro and Rigoberto Ríos-Estepa
Bioengineering 2022, 9(2), 78; https://doi.org/10.3390/bioengineering9020078 - 16 Feb 2022
Viewed by 2300
Abstract
Sigma factors and sigma factor-related mechanisms control antibiotic production in Streptomyces. In this contribution, the orf21 gene was overexpressed in the wild-type strain of Streptomyces clavuligerus ATCC2764, yielding S. clavuligerus/pIORF21, to further evaluate its regulatory effect on clavulanic acid (CA) biosynthesis [...] Read more.
Sigma factors and sigma factor-related mechanisms control antibiotic production in Streptomyces. In this contribution, the orf21 gene was overexpressed in the wild-type strain of Streptomyces clavuligerus ATCC2764, yielding S. clavuligerus/pIORF21, to further evaluate its regulatory effect on clavulanic acid (CA) biosynthesis under different culture medium conditions. The orf21 overexpression, regulated under the constitutive promoter ermE*, led to 2.6-fold increase in CA production in GSPG medium, and a 1.8-fold decrease using ISP medium. As for GYM and MYM media, S. clavuligerus/pIORF21 strain showed higher aerial mycelium production compared to control. Glycerol uptake rate profile was affected by orf21 overexpression. Furthermore, in GSPG, S. clavuligerus/pIORF21 slightly increased the expression of adpA and gcas genes, whilst, in ISP, the claR gene expression was drastically reduced, which is consistent with a decreased CA production, observed in this medium. These findings suggest the protein encoded by the orf21 gene plays a role in the regulation of CA biosynthesis as a response to the nutritional composition of the medium. Full article
(This article belongs to the Special Issue Strategies for the Efficient Development of Microbial Bioprocesses)
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16 pages, 6997 KiB  
Article
TCA Cycle and Its Relationship with Clavulanic Acid Production: A Further Interpretation by Using a Reduced Genome-Scale Metabolic Model of Streptomyces clavuligerus
by Howard Ramirez-Malule, Víctor A. López-Agudelo, David Gómez-Ríos, Silvia Ochoa, Rigoberto Ríos-Estepa, Stefan Junne and Peter Neubauer
Bioengineering 2021, 8(8), 103; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering8080103 - 22 Jul 2021
Cited by 5 | Viewed by 2765
Abstract
Streptomyces clavuligerus (S. clavuligerus) has been widely studied for its ability to produce clavulanic acid (CA), a potent inhibitor of β-lactamase enzymes. In this study, S. clavuligerus cultivated in 2D rocking bioreactor in fed-batch operation produced CA at comparable rates to [...] Read more.
Streptomyces clavuligerus (S. clavuligerus) has been widely studied for its ability to produce clavulanic acid (CA), a potent inhibitor of β-lactamase enzymes. In this study, S. clavuligerus cultivated in 2D rocking bioreactor in fed-batch operation produced CA at comparable rates to those observed in stirred tank bioreactors. A reduced model of S. clavuligerus metabolism was constructed by using a bottom-up approach and validated using experimental data. The reduced model was implemented for in silico studies of the metabolic scenarios arisen during the cultivations. Constraint-based analysis confirmed the interrelations between succinate, oxaloacetate, malate, pyruvate, and acetate accumulations at high CA synthesis rates in submerged cultures of S. clavuligerus. Further analysis using shadow prices provided a first view of the metabolites positive and negatively associated with the scenarios of low and high CA production. Full article
(This article belongs to the Special Issue Strategies for the Efficient Development of Microbial Bioprocesses)
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