12,668 results match your criteria Biotechnology and Bioengineering [Journal]


Transcriptome and Proteome analysis of steady-state in a perfusion CHO cell culture process.

Biotechnol Bioeng 2019 Apr 18. Epub 2019 Apr 18.

Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.

Long-term continuous protein production can be reached by perfusion operation. Through the continuous removal of waste metabolites and supply of nutrients, steady-state (SS) conditions are achieved after a certain transient period, where the conditions inside the reactor are not only uniform in space but also constant in time. Such stable conditions may have beneficial influences on the reduction of product heterogeneities. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/bit.26996
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http://dx.doi.org/10.1002/bit.26996DOI Listing
April 2019
6 Reads

Construction of second generation protease-deficient hosts of Bacillus subtilis for secretion of foreign proteins.

Biotechnol Bioeng 2019 Apr 16. Epub 2019 Apr 16.

Key Laboratory of Agricultural Environmental Microbiology, Ministry of Agriculture, College of Life Sciences, Nanjing Agricultural University, Nanjing, Jiangsu, People's Republic of China.

Although one of the major factors limiting the application of Bacillus subtilis as an expression host has been its production of at least eight extracellular proteases, researchers have also noticed that some proteases benefited the secretion of foreign proteins at times. Therefore, to maximize the yield of a foreign protein, the proteases should be selectively inactivated. This raises a new question that how to identify the favorable and unfavorable proteases for a target protein. Read More

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http://dx.doi.org/10.1002/bit.26992DOI Listing

Methyl ketone production by Pseudomonas putida is enhanced by plant-derived amino acids.

Biotechnol Bioeng 2019 Apr 14. Epub 2019 Apr 14.

Joint BioEnergy Institute, Emeryville, CA.

Plants are an attractive source of renewable carbon for conversion to biofuels and bio-based chemicals. Conversion strategies often use a fraction of the biomass, focusing on sugars from cellulose and hemicellulose. Strategies that use plant components such as aromatics and amino acids may improve the efficiency of biomass conversion. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/bit.26995
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http://dx.doi.org/10.1002/bit.26995DOI Listing
April 2019
1 Read

Sensitive detection of glucagon aggregation using amyloid fibril-specific antibodies.

Biotechnol Bioeng 2019 Apr 14. Epub 2019 Apr 14.

Departments of Pharmaceutical Sciences, Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.

Sensitive detection of protein aggregates is important for evaluating the quality of biopharmaceuticals and detecting misfolded proteins in several neurodegenerative diseases. However, it is challenging to detect extremely low concentrations (<10 ppm) of aggregated protein in the presence of high concentrations of natively-folded (soluble) protein. Glucagon, a peptide hormone used in the treatment of extreme hypoglycemia, is aggregation-prone and forms amyloid fibrils. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/bit.26994
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http://dx.doi.org/10.1002/bit.26994DOI Listing
April 2019
2 Reads

Lignocellulose Solubilization and Conversion by Extremely Thermophilic Caldicellulosiruptor bescii Improves by Maintaining Metabolic Activity.

Biotechnol Bioeng 2019 Apr 14. Epub 2019 Apr 14.

Department of Chemical and Biomolecular Engineering North Carolina State University, Raleigh, NC.

The extreme thermophile Caldicellulosiruptor bescii solubilizes and metabolizes the carbohydrate content of lignocellulose, a process that ultimately ceases because of biomass recalcitrance, accumulation of fermentation products, inhibition by lignin moieties, and reduction of metabolic activity. Deconstruction of low loadings of lignocellulose (5 g/l), either natural or transgenic, whether unpretreated or subjected to hydrothermal processing, by C. bescii typically results in less than 40% carbohydrate solubilization. Read More

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http://dx.doi.org/10.1002/bit.26993DOI Listing

New insights into the performance characteristics of the Planova-series hollow-fiber parvovirus filters using confocal and electron microscopy.

Biotechnol Bioeng 2019 Apr 14. Epub 2019 Apr 14.

Department of Chemical Engineering, The Pennsylvania State University, University Park, PA.

Virus filtration remains a critical step in the downstream process for the production of monoclonal antibodies and other mammalian cell-derived biotherapeutics. Recent studies have shown large differences in virus capture behavior of different virus filters, although the origin of these differences is still unclear. The objective of this study was to use confocal and scanning electron microscopy to directly evaluate the capture of virus-size nanoparticles in Planova 20N and BioEX hollow fiber virus filters. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/bit.26991
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http://dx.doi.org/10.1002/bit.26991DOI Listing
April 2019
1 Read

Ultra-high-throughput screening system for directed polymer binding peptide evolution.

Biotechnol Bioeng 2019 Apr 14. Epub 2019 Apr 14.

DWI - Leibniz-Institute for Interactive Materials, Forckenbeckstrasse 50 D-52074, Aachen, Germany.

Accumulation of plastics in the environment became a geological indicator of the Anthropocene era. An effective reduction of long-lasting plastics requires a treatment with microorganisms that release polymer-degrading enzymes. Polymer binding peptides function as adhesion promoters and enable a targeted binding of whole cells to polymer surfaces. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/bit.26990
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http://dx.doi.org/10.1002/bit.26990DOI Listing
April 2019
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Whole-bacterium ribosome display selection for isolation of highly specific anti-Staphyloccocus aureus Affitins for detection- and capture-based biomedical applications.

Biotechnol Bioeng 2019 Apr 14. Epub 2019 Apr 14.

CRCINA, INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes, France.

Detection and capture methods using antibodies have been developed to ensure identification of pathogens in biological samples. Though antibodies have many attractive properties, they also have limitations and there are needs to expand the panel of available affinity proteins with different properties. Affitins, that we developed from the Sul7d proteins, are a solid class of affinity proteins which can be used as substitutes to antibodies or to complement them. Read More

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http://dx.doi.org/10.1002/bit.26989DOI Listing

EWOD silicon biosensor for multiple nucleic acids analysis.

Biotechnol Bioeng 2019 Apr 9. Epub 2019 Apr 9.

STMicroelectronics, Stradale primosole, Catania.

In this paper, a miniaturized biosensor containing 96 silicon microchambers electroloaded with nano-volumes of liquid (EW-chip) is presented. The liquid electroloading is achieved by the appropriate modulation of interface properties. The surface chemistries have been studied to guarantee effective interface properties for both electrowetting on dielectric actuation and biocompatibility versus biochemical reactions. Read More

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http://dx.doi.org/10.1002/bit.26987DOI Listing

A thermoplastic microfluidic microphysiological system to recapitulate hepatic function and multi-cellular interactions.

Biotechnol Bioeng 2019 Apr 9. Epub 2019 Apr 9.

Draper, 555 Technology Square, Cambridge, MA.

Hepatic in vitro platforms ranging from multi-well cultures to bioreactors and microscale systems have been developed as tools to recapitulate cellular function and responses to aid in drug screening and disease model development. Recent developments in microfabrication techniques and cellular materials enabled fabrication of next-generation, advanced microphysiological systems (MPSs) that aim to capture the cellular complexity and dynamic nature of the organ presenting highly controlled extracellular cues to cells in a physiologically relevant context. Historically, MPSs have heavily relied on elastomeric materials in their manufacture, with unfavorable material characteristics ( such as lack of structural rigidity) limiting their use in high-throughput systems. Read More

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http://dx.doi.org/10.1002/bit.26986DOI Listing
April 2019
1 Read

Photosynthetic generation of heterologous terpenoids in cyanobacteria.

Biotechnol Bioeng 2019 Apr 9. Epub 2019 Apr 9.

Department of Plant and Microbial Biology, University of California, Berkeley, California.

The work aims to convert the secondary slow metabolism of the terpenoid biosynthetic pathway into a primary activity in cyanobacteria and to generate heterologous products using these photosynthetic microorganisms as cell factories. Case study is the production of the 10-carbon monoterpene β-phellandrene (PHL) in Synechocystis sp. PCC 6803 (Synechocystis). Read More

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http://dx.doi.org/10.1002/bit.26988DOI Listing
April 2019
1 Read

Novel, Linked Bioreactor System for Continuous Production of Biologics.

Biotechnol Bioeng 2019 Apr 5. Epub 2019 Apr 5.

Culture Process Development, Pfizer Inc., 1 Burtt Road, Andover, Massachusetts.

A novel, alternative intensified cell culture process comprised of a linked bioreactor system is presented. An N-1 perfusion bioreactor maintained cells in a highly proliferative state and provided a continuous inoculum source to a second bioreactor operating as a continuous-flow stirred-tank reactor (CSTR). An initial study evaluated multiple system steady-states by varying N-1 steady-state viable cell densities, N-1 to CSTR working volume ratios, and CSTR dilution rates. Read More

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http://dx.doi.org/10.1002/bit.26985DOI Listing
April 2019
2 Reads

Colorimetric biosensor using dual-amplification of enzyme-free reaction through universal hybridization chain reaction system.

Biotechnol Bioeng 2019 Apr 1. Epub 2019 Apr 1.

Department of Bioengineering and Nano-bioengineering, Incheon National University, Incheon, Korea.

On-site genetic detection needs to develop a sensitive and straightforward biosensor without special equipment, which can detect various genetic biomarkers. Hybridization chain reaction (HCR) amplifying signal isothermally could be considered as a good candidate for on-site detection. Here, we developed a novel genetic biosensor on the basis of enzyme-free dual-amplification of universal hybridization chain reaction (uHCR) and hemin/G-quadruplex horseradish peroxidase (HRP)-mimicking DNAzyme. Read More

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http://dx.doi.org/10.1002/bit.26978DOI Listing

Split-enzyme fragment as a single affinity tag that enables protein expression, purification, and functional assays.

Biotechnol Bioeng 2019 Apr 1. Epub 2019 Apr 1.

Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah.

Expressing, isolating, and characterizing recombinant proteins is crucial to many disciplines within the biological sciences. Different molecular tagging technologies have been developed to enable each individual step of protein production, from expression through purification and characterization. Monitoring the entire production process requires multiple tags or molecular interactions, because no individual tag has provided the comprehensive breadth of utility. Read More

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http://dx.doi.org/10.1002/bit.26980DOI Listing
April 2019
1 Read

Improvement of the acid resistance, catalytic efficiency, and thermostability of nattokinase by multisite-directed mutagenesis.

Biotechnol Bioeng 2019 Apr 1. Epub 2019 Apr 1.

Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, Jiangsu, China.

Nattokinase (NK) is a serine protease of the subtilisin family; as a potent fibrinolytic enzyme, it is potentially useful for thrombosis therapy. For NK to be applied as an oral medicine for the treatment of cardiovascular diseases, it must overcome the extremely acidic environments of the gastrointestinal tract despite its limited acidic stability. In this study, three strategies were adopted to improve the acid resistance of NK: (a) Surface charge engineering, (b) sequence alignment, and (c) mutation based on the literature. Read More

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http://dx.doi.org/10.1002/bit.26983DOI Listing
April 2019
1 Read

Enhancing 5-aminolevulinic acid tolerance and production by engineering the antioxidant defense system of Escherichia coli.

Biotechnol Bioeng 2019 Apr 1. Epub 2019 Apr 1.

Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.

5-Aminolevulinic acid (ALA) is a value-added compound with potential applications in the fields of agriculture and medicine. Although massive efforts have recently been devoted to building microbial producers of ALA through metabolic engineering, few studies focused on the cellular response and tolerance to ALA. In this study, we demonstrated that ALA caused severe cell damage and morphology change of Escherichia coli via generating reactive oxygen species (ROS), which were further determined to be mainly hydrogen peroxide and superoxide anion radical. Read More

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http://dx.doi.org/10.1002/bit.26981DOI Listing

An engineered mouse embryonic stem cell model with survivin as a molecular marker and EGFP as the reporter for high throughput screening of embryotoxic chemicals in vitro.

Biotechnol Bioeng 2019 Apr 1. Epub 2019 Apr 1.

William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, 151 West Woodruff Avenue, Columbus, Ohio.

Embryonic stem cell test (EST) is the only generally accepted in vitro method for assessing embryotoxicity without animal sacrifice. However, the implementation and application of EST for regulatory embryotoxicity screening are impeded by its technical complexity, long testing period, and limited endpoint data. In this study, a high throughput embryotoxicity screening based on mouse embryonic stem cells (mESCs) expressing enhanced green fluorescent protein (EGFP) driven by a human survivin promoter and a human cytomegalovirus promoter, respectively, was developed. Read More

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http://dx.doi.org/10.1002/bit.26977DOI Listing
April 2019
1 Read

Real-time monitoring and model-based prediction of purity and quantity during a chromatographic capture of fibroblast growth factor 2.

Biotechnol Bioeng 2019 Apr 1. Epub 2019 Apr 1.

Austrian Centre of Industrial Biotechnology, Vienna, Austria.

Process analytical technology combines understanding and control of the process with real-time monitoring of critical quality and performance attributes. The goal is to ensure the quality of the final product. Currently, chromatographic processes in biopharmaceutical production are predominantly monitored with UV/Vis absorbance and a direct correlation with purity and quantity is limited. Read More

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http://dx.doi.org/10.1002/bit.26984DOI Listing

Effect of gene copy number and chaperone coexpression on recombinant hydrophobin HFBI biosurfactant production in Pichia pastoris.

Biotechnol Bioeng 2019 Apr 1. Epub 2019 Apr 1.

Department of Biomedical Engineering, University of Virginia, Thornton Hall, Charlottesville, Virginia.

Hydrophobins are small highly surface-active fungal proteins with potential as biosurfactants in a wide array of applications. However, practical implementation of hydrophobins at large scale has been hindered by low recombinant yields. In this study, the effects of increasing hydrophobin gene copy number and overexpressing endoplasmic reticulum resident chaperone proteins Kar2p, Pdi1p, and Ero1p were explored as a means to enhance recombinant yields of the class II hydrophobin HFBI in the eukaryotic expression host Pichia pastoris. Read More

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http://dx.doi.org/10.1002/bit.26982DOI Listing
April 2019
2 Reads
4.126 Impact Factor

Genetic and chemical approaches for surface charge engineering of enzymes and their applicability in biocatalysis: A review.

Biotechnol Bioeng 2019 Mar 30. Epub 2019 Mar 30.

Teknologisk institut, Kongsvang Allé 29, Aarhus, DK.

Surface charge engineering has received considerable interest from the scientific and industrial community the last decades. Although it was previously hypothesized that the surface charge-charge interactions were not a fundamental force to determine protein folding and stability, many studies today show that surface charge plays a key role determining protein structure and activity. This review aims to i) highlight the value of surface charged engineering of proteins to improve enzyme stability and activity in aqueous media and in the presence of ionic liquids, and organic solvents, ii) describe the existing approaches (genetic engineering or chemical modifications) for surface charged engineering, and iii) demonstrate the applicability of these surface charged enzymes in biocatalysis. Read More

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http://dx.doi.org/10.1002/bit.26979DOI Listing

Quantitative Characterization of the Regulation of Iron Metabolism in Glioblastoma Stem-Like Cells using Magnetophoresis.

Biotechnol Bioeng 2019 Mar 24. Epub 2019 Mar 24.

William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, 470 CBEC 151 West Woodruff Avenue, Columbus, OH.

This study focuses on different iron regulation mechanisms of glioblastoma (GBM) cancer stem-like cells (CSCs) and non-stem tumor cells (NSTCs) using multiple approaches: cell viability, density and magnetophoresis. GBM CSCs and NSTCs were exposed to elevated iron concentration, and their magnetic susceptibility was measured using Single Cell Magnetophoresis (SCM), which tracks the magnetic and settling velocities of thousands of individual cells passing through the magnetic field with a constant energy gradient. Our results consistently demonstrate that GBM NSTCs have higher magnetic susceptibility distribution at increased iron concentration compared to CSCs, and we speculate that it is because CSCs have the ability to store a high amount of iron in ferritin, whereas the free iron ions inside the NSTCs lead to higher magnetic susceptibility and reduced cell viability and growth. Read More

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http://dx.doi.org/10.1002/bit.26973DOI Listing

Direct capture and conversion of CO from air by growing a cyanobacterial consortium at pH up to 11.2.

Biotechnol Bioeng 2019 Mar 24. Epub 2019 Mar 24.

Department of Geoscience, University of Calgary, Calgary, Alberta, Canada.

Bioenergy with carbon capture and storage (BECCS) is recognized as a potential negative emission technology, needed to keep global warming within safe limits. With current technologies, large-scale implementation of BECCS would compromise food production. Bioenergy derived from phototrophic microorganisms, with direct capture of CO from air, could overcome this challenge and become a sustainable way to realize BECCS. Read More

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http://dx.doi.org/10.1002/bit.26974DOI Listing

Growth factor sustained delivery from poly-lactic-co-glycolic acid microcarriers and its mass transfer modeling by finite element in a dynamic and static three-dimensional environment bioengineered with stem cells.

Biotechnol Bioeng 2019 Mar 24. Epub 2019 Mar 24.

Department of Industrial Engineering, University of Salerno, Fisciano, SA, Italy.

Poly-lactic-co-glycolic acid (PLGA) microcarriers (0.8 ± 0.2 μm) have been fabricated with a load of 20 μg/g by an emulsion-based-proprietary technology to sustained deliver human bone morphogenetic protein 2 (hBMP2), a growth factor largely used for osteogenic induction. Read More

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http://dx.doi.org/10.1002/bit.26975DOI Listing
March 2019
1 Read

Synthesis of polyketides from low cost substrates by the thermotolerant yeast Kluyveromyces marxianus.

Biotechnol Bioeng 2019 Mar 24. Epub 2019 Mar 24.

Department of Chemical and Biomolecular Engineering, University of California, Irvine, CA, USA.

Kluyveromyces marxianus is a promising nonconventional yeast for biobased chemical production due to its rapid growth rate, high TCA cycle flux, and tolerance to low pH and high temperature. Unlike S. cerevisiae, K. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/bit.26976
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http://dx.doi.org/10.1002/bit.26976DOI Listing
March 2019
3 Reads

Efficient production of poly γ-d-glutamic acid from the bloom-forming green macroalgae, Ulva sp., by Bacillus sp. SJ-10.

Biotechnol Bioeng 2019 Mar 18. Epub 2019 Mar 18.

Department of Biotechnology, College of Fisheries Science, Pukyong National University, Busan, Republic of Korea.

Numerous studies on poly γ-d-glutamicacid (γ-PGA) production have investigated terrestrial renewable sources for reducing production costs, but there are no studies using waste marine resources so far. We aimed to develop a cost-effective production method of γ-d-PGA by Bacillus sp. SJ-10 using green macroalgae (Ulva sp. Read More

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http://dx.doi.org/10.1002/bit.26966DOI Listing

Reduced apoptosis in Chinese hamster ovary cells via optimized CRISPR interference.

Biotechnol Bioeng 2019 Mar 18. Epub 2019 Mar 18.

The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Denmark.

Chinese hamster ovary (CHO) cells are widely used for biopharmaceutical protein production. One challenge limiting CHO cell productivity is apoptosis stemming from cellular stress during protein production. Here we applied CRISPR interference (CRISPRi) to downregulate the endogenous expression of apoptotic genes Bak, Bax, and Casp3 in CHO cells. Read More

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http://dx.doi.org/10.1002/bit.26969DOI Listing
March 2019
3 Reads
4.126 Impact Factor

Adenovirus 5 recovery using nanofiber ion-exchange adsorbents.

Biotechnol Bioeng 2019 Mar 18. Epub 2019 Mar 18.

Department of Biochemical Engineering, University College London, London, United Kingdom.

Viral vectors such as adenovirus have successful applications in vaccines and gene therapy but the manufacture of the high-quality virus remains a challenge. It is desirable to use the adsorption-based chromatographic separations that so effectively underpin the therapeutic protein manufacture. However fundamental differences in the size and stability of this class of product mean it is necessary to revisit the design of sorbent's morphology and surface chemistry. Read More

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http://dx.doi.org/10.1002/bit.26972DOI Listing

An epitope-directed antibody affinity maturation system utilizing mammalian cell survival as readout.

Biotechnol Bioeng 2019 Mar 18. Epub 2019 Mar 18.

Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.

Upon developing therapeutically potent antibodies, there are significant requirements, such as increasing their affinity, regulating their epitope, and using native target antigens. Many antibody selection systems, such as a phage display method, have been developed, but it is still difficult to fulfill these requirements at the same time. Here, we propose a novel epitope-directed antibody affinity maturation system utilizing mammalian cell survival as readout. Read More

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http://dx.doi.org/10.1002/bit.26965DOI Listing
March 2019
1 Read

Optimized protocol for the hepatic differentiation of induced pluripotent stem cells in a fluidic microenvironment.

Biotechnol Bioeng 2019 Mar 18. Epub 2019 Mar 18.

Laboratory for Integrated Micro Mechatronic Systems, CNRS UMI 2820, Institute of Industrial Science, The University of Tokyo, Tokyo, Japan.

In the present study, we evaluated the performance of different protocols for the hepatic differentiation of human-induced pluripotent stem cells (hiPSCs) in microfluidic biochips. Strategies for complete and partial on-chip differentiation were tested. Unlike full on-chip differentiation, the transfer of iPSCs from Petri dishes to biochips during the differentiation process produced a heterogeneous tissue with enhanced hepatic features compared with control cultures in Petri dishes. Read More

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http://dx.doi.org/10.1002/bit.26970DOI Listing
March 2019
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Immunoglobulin G transport increases in an in vitro blood-brain barrier model with amyloid-β and with neuroinflammatory cytokines.

Biotechnol Bioeng 2019 Mar 18. Epub 2019 Mar 18.

Department of Chemical and Biomolecular Engineering, Delaware Biotechnology Institute, University of Delaware, Newark, Delaware.

Immunotherapies are a promising strategy for the treatment of neurological diseases such as Alzheimer's disease (AD), however, transport of antibodies to the brain is severely restricted by the blood-brain barrier (BBB). Furthermore, molecular transport at the BBB is altered in disease, which may affect the mechanism and quantity of therapeutic antibody transport. To better understand the transport of immunotherapies at the BBB in disease, an in vitro BBB model derived from human induced pluripotent stem cells (iPSCs) was used to investigate the endocytic uptake route of immunoglobulin G (IgG). Read More

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http://dx.doi.org/10.1002/bit.26967DOI Listing
March 2019
7 Reads
4.126 Impact Factor

Impact of depth filtration on disulfide bond reduction during downstream processing of monoclonal antibodies from CHO cell cultures.

Biotechnol Bioeng 2019 Mar 18. Epub 2019 Mar 18.

BioProcess Development, Bristol-Myers Squibb Co., Seattle, Washington.

Monoclonal antibody interchain disulfide bond reduction was observed in a Chinese Hamster Ovary manufacturing process that used single-use technologies. A similar reduction has been reported for processes that involved high mechanical shear recovery unit operations, such as continuous flow centrifugation and when the clarified harvest was stored under low dissolved oxygen (DO) conditions (Trexler-Schmidt et al., 2010. Read More

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http://dx.doi.org/10.1002/bit.26964DOI Listing
March 2019
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Coping with inadvertent lysis of Escherichia coli cultures: Strains resistant to lysogeny and infection by the stealthy lysogenic phage Φ80.

Biotechnol Bioeng 2019 Mar 18. Epub 2019 Mar 18.

Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois.

Phage Φ80 can infect Escherichia coli in a stealthy manner and persist by forming lysogens. Such Φ80 lysogens are fairly common and often go undetected unless the host is grown at temperatures below 37°C. Since low growth temperatures are required for growing temperature-sensitive mutants and often preferred for large-scale applications such as protein production, Φ80-resistant strains would be useful. Read More

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http://dx.doi.org/10.1002/bit.26971DOI Listing

Investigation of cathepsin D-mAb interactions using a combined experimental and computational tool set.

Biotechnol Bioeng 2019 Mar 18. Epub 2019 Mar 18.

Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York.

Cathepsin D has been identified as a challenge to remove in downstream bioprocessing of monoclonal antibodies (mAbs) due to interactions with some mAbs. This study focused on investigating the mechanisms of interaction between cathepsin D and two industrial mAbs using a combined experimental and computational approach. Surface plasmon resonance was used to study the impact of pH and salt concentration on these protein-protein interactions. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/bit.26968
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http://dx.doi.org/10.1002/bit.26968DOI Listing
March 2019
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Enhanced electron transfer of different mediators for strictly opposite shifting of metabolism in Clostridium pasteurianum grown on glycerol in a new electrochemical bioreactor.

Biotechnol Bioeng 2019 Mar 2. Epub 2019 Mar 2.

Institute of Bioprocess and Biosystems Engineering, Hamburg University of Technology Denickestrasse, Hamburg, Germany.

Microbial electrosynthesis or electro-fermentation in bioelectrochemical systems (BES) have recently received much attention. Here, we demonstrate with the glycerol metabolism by Clostridium pasteurianum that H from in situ water electrolysis, especially in combination with a redox mediator, provides a simple and flexible way for shifting product selectivity and enhancing product yield in the fermentation process. In particular, we report and quantify for the first time strictly different effects of Neutral Red (NR) and the barely studied redox mediator Brilliant Blue (BB) on the growth and product formation of C. Read More

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http://dx.doi.org/10.1002/bit.26963DOI Listing
March 2019
1 Read

Establishing synthesis pathway-host compatibility via enzyme solubility.

Biotechnol Bioeng 2019 Feb 25. Epub 2019 Feb 25.

Department of Computer Science, Tufts University, Medford, Massachusetts.

Current pathway synthesis tools identify possible pathways that can be added to a host to produce the desired target molecule through the exploration of abstract metabolic and reaction network space. However, not many of these tools explore gene-level information required to physically realize the identified synthesis pathways, and none explore enzyme-host compatibility. Developing tools that address this disconnect between abstract reactions/metabolic design space and physical genetic sequence design space will enable expedited experimental efforts that avoid exploring unprofitable synthesis pathways. Read More

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http://dx.doi.org/10.1002/bit.26959DOI Listing
February 2019
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Transcriptomic analysis of IgG4 Fc-fusion protein degradation in a panel of clonally-derived CHO cell lines using RNASeq.

Biotechnol Bioeng 2019 Feb 25. Epub 2019 Feb 25.

National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin, Ireland.

In this study, we report an investigation of a panel of clonally-derived Chinese hamster ovary (CHO) cell lines exhibiting variability in the proportion of full-length IgG4 Fc-fusion protein produced. The recombinant protein was found to be degraded during cell culture into four shorter "clipped" species (three of the four cleavage sites occurred at arginine residues) and preliminary analyses suggested that a host cell enzyme was responsible for proteolysis. To identify the specific enzyme responsible, RNA sequencing was used to identify gene expression differences between the cell lines with a "high" and "low" clipping phenotype. Read More

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http://dx.doi.org/10.1002/bit.26958DOI Listing
February 2019
8 Reads

Model-based optimization of antibody galactosylation in CHO cell culture.

Biotechnol Bioeng 2019 Feb 25. Epub 2019 Feb 25.

Department of Chemical Engineering, Imperial College London, United Kingdom.

Exerting control over the glycan moieties of antibody therapeutics is highly desirable from a product safety and batch-to-batch consistency perspective. Strategies to improve antibody productivity may compromise quality, while interventions for improving glycoform distribution can adversely affect cell growth and productivity. Process design therefore needs to consider the trade-off between preserving cellular health and productivity while enhancing antibody quality. Read More

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http://dx.doi.org/10.1002/bit.26960DOI Listing
February 2019
2 Reads

Impact of protein blocking on enzymatic saccharification of bagasse from sugarcane clones.

Biotechnol Bioeng 2019 Feb 25. Epub 2019 Feb 25.

Laboratory of Renewable Resources Engineering, Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, Indiana.

Lignin plays an important functional and structural role in plants, but also contributes to the recalcitrance of lignocellulosic biomass to hydrolysis. This study addresses the influence of lignin in hydrolysis of sugarcane bagasse from conventional bred lines (UFV260 and UFV204) that were selected from 432 field-grown clones. In addition to higher sugar production, bagasse clone UFV204 had a small, but statistically significant, lower insoluble lignin content compared with clone UFV260 (15. Read More

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http://dx.doi.org/10.1002/bit.26962DOI Listing
February 2019
2 Reads

Three-dimensional microfluidic tumor-macrophage system for breast cancer cell invasion.

Biotechnol Bioeng 2019 Feb 25. Epub 2019 Feb 25.

Graduate School at Shenzhen, Tsinghua University, Shenzhen, P.R. China.

The recrudescence of breast cancer can partly be attributed to poor understanding of the early steps and the mechanisms involved in breast cancer metastasis, especially how tumor inflammatory cells including tumor-associated macrophages (TAM) affect invasion process. However, invasion-related biological studies in traditional in vitro assays or in vivo models are challenging due to the arduousness in establishing models that precisely reproduce the tumor invasion environment. To this end, we proposed a juxtaposed dual-layer cell-loaded hydrogels biomimetic microfluidic system and formed monolayer size-selective permeable vascular endothelial barriers besides the dual layer to mimic mammalian blood vessels. Read More

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http://dx.doi.org/10.1002/bit.26961DOI Listing
February 2019
1 Read

Vitamins in cell culture media: Stability and stabilization strategies.

Biotechnol Bioeng 2019 Feb 21. Epub 2019 Feb 21.

Upstream R&D, Life Science Division, Merck KGaA, Darmstadt, Germany.

Nowadays, chemically defined cell culture media (CCM) have replaced serum- and hydrolysate-based media that rely on complex ingredients, such as yeast extracts or peptones. Benefits include a significantly lower lot-to-lot variability, more efficient manufacturing by reduction to essential components, and the ability to exclude components that may negatively influence growth, viability, or productivity. Even though current chemically defined CCMs provide an excellent basis for various mammalian biotechnological processes, vitamin instabilities are known to be a key factor contributing to the variabilities still present in liquid CCM as well as to short storage times. Read More

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http://dx.doi.org/10.1002/bit.26942DOI Listing
February 2019

A comparison of human mesenchymal stem cell osteogenesis in poly(ethylene glycol) hydrogels as a function of MMP-sensitive crosslinker and crosslink density in chemically defined medium.

Biotechnol Bioeng 2019 Feb 18. Epub 2019 Feb 18.

Department of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado.

This study investigated osteogenesis of human mesenchymal stem cells encapsulated in matrix-metalloproteinase (MMP)-sensitive poly(ethylene glycol) (PEG) hydrogels in chemically defined medium (10 ng/ml bone morphogenic factor-2). Thiol-norbornene photoclick hydrogels were formed with CRGDS and crosslinkers of PEG dithiol (nondegradable), CVPLS-LYSGC (P1) or CRGRIGF-LRTDC (P2; dash indicates cleavage site) at two crosslink densities. Exogenous MMP-2 degraded P1 and P2 hydrogels similarly. Read More

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http://dx.doi.org/10.1002/bit.26957DOI Listing
February 2019
2 Reads

An X-ray microtomography-based method for detailed analysis of the three-dimensional morphology of fungal pellets.

Biotechnol Bioeng 2019 Feb 15. Epub 2019 Feb 15.

Technical University of Munich, School of Life Sciences Weihenstephan, Chair of Process Systems Engineering, Freising, Germany.

Filamentous fungi are widely used in the production of biotechnological compounds. Since their morphology is strongly linked to productivity, it is a key parameter in industrial biotechnology. However, identifying the morphological properties of filamentous fungi is challenging. Read More

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http://dx.doi.org/10.1002/bit.26956DOI Listing
February 2019
1 Read

Challenging the workhorse: Comparative analysis of eukaryotic micro-organisms for expressing monoclonal antibodies.

Biotechnol Bioeng 2019 Feb 10. Epub 2019 Feb 10.

Engineering & Technology, Biogen, Cambridge, Massachusetts.

For commercial protein therapeutics, Chinese hamster ovary (CHO) cells have an established history of safety, proven capability to express a wide range of therapeutic proteins and high volumetric productivities. Expanding global markets for therapeutic proteins and increasing concerns for broadened access of these medicines has catalyzed consideration of alternative approaches to this platform. Reaching these objectives likely will require an order of magnitude increase in volumetric productivity and a corresponding reduction in the costs of manufacture. Read More

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http://dx.doi.org/10.1002/bit.26951DOI Listing
February 2019
3 Reads

CRISPR-Cas9 nickase-assisted base editing in the solvent producer Clostridium beijerinckii.

Biotechnol Bioeng 2019 Feb 10. Epub 2019 Feb 10.

Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

Clostridium beijerinckii is a potentially important industrial microorganism as it can synthesize valuable chemicals and fuels from various carbon sources. The establishment of convenient to use, effective gene tools with which the organism can be rapidly modified is essential if its full potential is to be realized. Here, we developed a genomic editing tool (pCBEclos) for use in C. Read More

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http://dx.doi.org/10.1002/bit.26949DOI Listing
February 2019
11 Reads

Improving bioreactor production of a recombinant glycoprotein in Escherichia coli: Effect of specific growth rate on protein glycosylation and specific productivity.

Biotechnol Bioeng 2019 Feb 10. Epub 2019 Feb 10.

Instituto de Investigaciones Biotecnológicas Dr. Rodolfo A. Ugalde, Instituto Tecnológico de Chascomús (IIB-INTECH), Universidad Nacional de San Martín, CONICET, San Martín, Buenos Aires, Argentina.

In the last decades bacterial glycoengineering emerged as a new field as the result of the ability to transfer the Campylobacter jejuni N- glycosylation machinery into Escherichia coli for the production of recombinant glycoproteins that can be used as antigens for diagnosis, vaccines, and therapeutics. However, the identification of critical parameters implicated in the production process and its optimization to jump to a productive scale is still required. In this study, we developed a dual expression glycosylation vector for the production of the recombinant glycoprotein AcrA-O157, a novel antigen that allows the serodiagnosis of the infection with enterohemorrhagic E. Read More

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http://dx.doi.org/10.1002/bit.26953DOI Listing
February 2019
6 Reads

Generation and characterization of a functional human adipose-derived multipotent mesenchymal stromal cell line.

Biotechnol Bioeng 2019 Feb 10. Epub 2019 Feb 10.

Institute of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria.

Multipotent mesenchymal stromal cells (MSC) and MSC-derived products have emerged as promising therapeutic tools. To fully exploit their potential, further mechanistic studies are still necessary and bioprocessing needs to be optimized, which requires an abundant supply of functional MSC for basic research. To address this need, here we used a novel technology to establish a human adipose-derived MSC line with functional characteristics representative of primary MSC. Read More

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http://dx.doi.org/10.1002/bit.26950DOI Listing
February 2019
5 Reads

An integrated platform for mucin-type O-glycosylation network generation and visualization.

Biotechnol Bioeng 2019 Feb 10. Epub 2019 Feb 10.

Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, Minnesota.

Mucin-type O-glycans have profound effects on the structure and stability of glycoproteins. O-Glycans on the cell surface proteins also modulate the cell's interactions with the surrounding environments and other cells. The synthetic pathway of O-glycans involves a large number of enzymes with diverse substrate specificity. Read More

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http://dx.doi.org/10.1002/bit.26952DOI Listing
February 2019
1 Read

Developing scalable cultivation systems of hepatic spheroids for drug metabolism via genomic and functional analyses.

Biotechnol Bioeng 2019 Feb 9. Epub 2019 Feb 9.

Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.

Spheroids, a widely used three-dimensional (3D) culture model, are standard in hepatocyte culture as they preserve long-term hepatocyte functionality and enhance survivability. In this study, we investigated the effects of three operation modes in 3D culture - static, orbital shaking, and under vertical bidirectional flow using spheroid forming units (SFUs) on hepatic differentiation and drug metabolism to propose the best for mass production of functionally enhanced spheroids. Spheroids in SFUs exhibited increased hepatic gene expression, albumin secretion, and cytochrome P450 3A4 (CYP3A4) activity during the differentiation period (12 days). Read More

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http://dx.doi.org/10.1002/bit.26954DOI Listing
February 2019

Modeling, simulations, and optimization of smooth muscle cell tissue engineering for the production of vascular grafts.

Biotechnol Bioeng 2019 Feb 9. Epub 2019 Feb 9.

National Physical Laboratory, Teddington, Middlesex, UK.

The paper presents a transient, continuum, two-phase model of the tissue engineering in fibrous scaffolds, including transport equations for the flowing culture medium, nutrient and cell concentration with transverse and in-plane diffusion and cell migration, a novel feature of local in-plane transport across a phenomenological pore and innovative layer-by-layer cell filling approach. The model is successfully validated for the smooth muscle cell tissue engineering of a vascular graft using crosslinked, electrospun gelatin fiber scaffolds for both static and dynamic cell culture, the latter in a dynamic bioreactor with a rotating shaft on which the tubular scaffold is attached. Parametric studies evaluate the impact of the scaffold microstructure, cell dynamics, oxygen transport, and static or dynamic conditions on the rate and extent of cell proliferation and depth of oxygen accessibility. Read More

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http://dx.doi.org/10.1002/bit.26955DOI Listing
February 2019
1 Read

Improved CRISPR-Cas12a-assisted one-pot DNA editing method enables seamless DNA editing.

Biotechnol Bioeng 2019 Feb 7. Epub 2019 Feb 7.

Department of Gastroenterology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China.

As the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas12a (previously known as Cpf1) system cleaves double-stranded DNA and produces a sticky end, it could serve as a useful tool for DNA assembly/editing. To broaden its application, a variety of engineered FnCas12a proteins are generated with expanded protospacer adjacent motif (PAM) requirements. Two variants (FnCas12a-EP15 and EP16) increased the targeting range of FnCas12a by approximately fourfold. Read More

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http://doi.wiley.com/10.1002/bit.26938
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http://dx.doi.org/10.1002/bit.26938DOI Listing
February 2019
43 Reads
4.126 Impact Factor