2,360 results match your criteria Biotechnology Journal[Journal]


Application of the Bradford assay for cell lysis quantification: Residual protein content (RPC) in cell culture supernatants.

Biotechnol J 2019 Apr 14:e1800714. Epub 2019 Apr 14.

DBT - University of Natural Resources and Life Sciences (BOKU), Vienna, Austria.

Frequently measured mammalian cell culture process indicators include viability and total cell concentration. Cell lysis, an additional important process characteristic that substantially contributes to overall product purity profiles is often not addressed in detail; however, quantitative information on cell lysis could be very useful in the process in terms of monitoring and control. Lysis is commonly indirectly determined via the amount of DNA or the activity of lactate dehydrogenase in supernatant samples. Read More

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http://dx.doi.org/10.1002/biot.201800714DOI Listing

Engineered Skin Tissue Equivalents for Product Evaluation and Therapeutic Applications.

Biotechnol J 2019 Apr 12:e1900022. Epub 2019 Apr 12.

Department of Orthopaedic Surgery, , University of Connecticut Health, 263 Farmington Ave, Farmington, CT, USA.

This article reviews the current status of skin tissue equivalents that have emerged as relevant tools in commercial and therapeutic product development applications. Due to rise of animal welfare concerns, numerous companies have designed skin model alternatives to assess the efficacy of pharmaceutical, skincare and cosmetic products in an in vitro setting, decreasing the dependency on such methods. Several validated test methods are performed on such models to investigate various characteristics including skin irritation, permeation, corrosion and hydration, genotoxicity and absorption. Read More

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http://dx.doi.org/10.1002/biot.201900022DOI Listing
April 2019
5 Reads

Bioenergy and Biorefinery: feedstock, biotechnological conversion and products.

Biotechnol J 2019 Apr 10:e1800494. Epub 2019 Apr 10.

Department of Science, Technology and Innovation, Graduate School of Science, Technology and Innovation, Kobe University, 1-1 Rokkodai, Nada-ku, Kobe, Japan.

Biorefinery has been suggested to provide relevant substitutes to a number of fossil products. Feedstocks and conversion technologies have however, been the bottle-neck to the realization of this concept. Herein, feedstocks and bioconversion technologies under biorefinery have been reviewed. Read More

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http://dx.doi.org/10.1002/biot.201800494DOI Listing

The transcriptome and flux profiling of Crabtree-negative hydroxy acid producing strains of Saccharomyces cerevisiae reveals changes in the central carbon metabolism.

Biotechnol J 2019 Apr 10:e1900013. Epub 2019 Apr 10.

The Novo Nordisk Foundation for Biosustainability, Technical University of Denmark, Building 220, Kongens Lyngby, Denmark.

Saccharomyces cerevisiae is a yeast cell factory of choice for the production of many bio-based chemicals. However, it is also a Crabtree-positive yeast and so it shuttles a large portion of carbon into ethanol, even under aerobic conditions. To minimise the carbon loss, ethanol formation can be eliminated by deleting pyruvate decarboxylase (PDC) activity. Read More

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http://dx.doi.org/10.1002/biot.201900013DOI Listing

Genetic and epigenetic variation across genes involved in energy metabolism and mitochondria of Chinese Hamster Ovary cell lines.

Biotechnol J 2019 Apr 10:e1800681. Epub 2019 Apr 10.

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

The increasing demand for biopharmaceutical products drives the search for efficient cell factories that are able to sustainably support rapid growth, high productivity and product quality. As all of these depend on the generation of energy, we here investigate the genomic variation in nuclear genes associated with mitochondria and energy metabolism, as well as in the mitochondrial genome of 14 cell lines. The variants called, both from the mitochondrial genome alone or from the combination with nuclear mitochondria-associated genes enable reliable tracing of lineages. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/biot.2018006
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http://dx.doi.org/10.1002/biot.201800681DOI Listing
April 2019
6 Reads

Towards self-regulated bioprocessing: a compact benchtop bioreactor system for monitored and controlled 3D cell and tissue culture.

Biotechnol J 2019 Apr 9:e1800545. Epub 2019 Apr 9.

Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium.

Bioreactors are crucial tools for the manufacturing of living cell based tissue engineered products. However, to reach the market successfully, higher degrees of automation as well as a decreased footprint still need to be reached. In this study, we assessed the use of a benchtop bioreactor for in-vitro perfusion culture of scaffold based TE constructs. Read More

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http://dx.doi.org/10.1002/biot.201800545DOI Listing

Sacrificial Bioprinting of A Mammary Ductal Carcinoma Model.

Biotechnol J 2019 Apr 9:e1700703. Epub 2019 Apr 9.

Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, USA.

Cancer tissue engineering has remained challenging due to the limitation of the conventional biofabrication techniques to model the complex cancer microenvironment. Here we report the utilization of a sacrificial bioprinting strategy to generate biomimetic mammary duct-like structures within a hydrogel matrix, which was further populated with breast cancer cells, to model the genesis of ductal carcinoma and its subsequent outward invasion. This bioprinted mammary ductal carcinoma model provides a proof-of-concept demonstration of the value of using the sacrificial bioprinting technique for engineering biologically relevant cancer models, which may be possibly extended to other cancer types where duct-like structures are involved. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/biot.2017007
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http://dx.doi.org/10.1002/biot.201700703DOI Listing
April 2019
1 Read

3D primary hepatocyte culture systems for analyses of liver diseases, drug metabolism and toxicity: Emerging culture paradigms and applications.

Biotechnol J 2019 Apr 8:e1800347. Epub 2019 Apr 8.

Department of Physiology and Pharmacology, Section of Pharmacogenetics, Karolinska Institutet, SE-171 77, Stockholm, Sweden.

Recent research has shown that the maintenance of relevant liver functions ex vivo requires models in which the cells exhibit an in vivo-like phenotype, often achieved by reconstitution of appropriate cellular interactions. Multiple different models have been presented that differ in the cells utilized, media and culture conditions. Furthermore, several technologically different approaches have been presented including bioreactors, chips and plate-based systems in fluidic or static media constituting of chemically diverse materials. Read More

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http://dx.doi.org/10.1002/biot.201800347DOI Listing

Minimizing the influence of fluorescent tags on IgG partition in PEG-salt aqueous two-phase systems for rapid screening applications.

Biotechnol J 2019 Apr 8:e1800640. Epub 2019 Apr 8.

IBB - Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal.

Aqueous two-phase extraction (ATPE) has been showing significant potential in the biopharmaceutical industry, allowing the selective separation of high-value proteins directly from unclarified cell culture supernatants. In this context, effective high-throughput screening tools are critical to perform a rapid empirical optimization of operating conditions. Microfluidic ATPE screening devices in particular, coupled with fluorescence microscopy to continuously monitor the partition of fluorophore labelled proteins, have been recently demonstrated to provide short diffusion distances and rapid partition, using minimal reagent volumes. Read More

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http://dx.doi.org/10.1002/biot.201800640DOI Listing

[Scalable Manufacturing of Human Mesenchymal Stromal Cells in the Vertical-Wheel™ Bioreactor System: An Experimental and Economic Approach].

Biotechnol J 2019 Apr 4:e1800716. Epub 2019 Apr 4.

Department of Bioengineering and iBB, Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.

Mesenchymal stromal cells (MSC) hold great promise for tissue engineering applications and cell-based therapies. Large cell doses (>1x10 cells/kg) and Good Manufacturing Practices (GMP)-compliant processes are however required for clinical purposes. Here, a serum- and xenogeneic-free (S/XF) microcarrier-based culture system was established for the expansion of human umbilical cord matrix (UCM)- and adipose tissue (AT)-derived MSC using the Vertical-Wheel™ system (PBS-0. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/biot.2018007
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http://dx.doi.org/10.1002/biot.201800716DOI Listing
April 2019
1 Read

Antibody binding heterogeneity of Protein A resins.

Biotechnol J 2019 Apr 4:e1800632. Epub 2019 Apr 4.

CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, Covilhã, Portugal.

Protein A affinity chromatography is a core unit operation in antibody manufacturing. Nevertheless, there is not enough understanding of in-column antibody adsorption in the Protein A capture step. This work aims to investigate in situ the establishment of an antibody (trastuzumab) layer during Protein A chromatography both in terms of energetic contributions and uptake kinetics. Read More

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http://dx.doi.org/10.1002/biot.201800632DOI Listing
April 2019
1 Read

The promises and the challenges of biotransformations in micro-flow.

Biotechnol J 2019 Apr 4:e1800580. Epub 2019 Apr 4.

University of Ljubljana, Faculty of Chemistry and Chemical Technology, Ljubljana, Slovenia.

The challenges of transition towards the post-petroleum world shed light on the biocatalysis as the most sustainable way for the valorization of bio-based raw materials. However, its industrial exploitation strongly relies on integration with innovative technologies such as micro-scale processing. Micro-flow devices remarkably accelerate biocatalyst screening and engineering, as well as process parameters evaluation, and intensify biocatalytic processes in multiphase systems. Read More

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http://dx.doi.org/10.1002/biot.201800580DOI Listing

Prediction of quantity and purity of an antibody capture process in real-time.

Biotechnol J 2019 Apr 4:e1800521. Epub 2019 Apr 4.

Austrian Centre of Industrial Biotechnology, Muthgasse 18, Vienna, Austria.

Regulatory recommendations for quality by design instead of quality by testing raised increasing interest in new sensor technologies. We have developed an online monitoring system for downstream processes, which is based on an array of online detectors. Besides the standard detectors (UV, pH, conductivity), our chromatographic workstation was equipped with a fluorescence and a mid-infrared spectrometer, a light scattering and a refractive index detector. Read More

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http://dx.doi.org/10.1002/biot.201800521DOI Listing

Experimental Evaluation of the Impact of Intrinsic Process Parameters on the Performance of a Continuous Chromatographic Polishing Unit (MCSGP).

Biotechnol J 2019 Mar 30:e1800732. Epub 2019 Mar 30.

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

The semi-continuous twin-column MCSGP process improves the trade-off between purity and yield encountered in traditional batch chromatography, while its complexity in terms of hardware requirements and process design is reduced in comparison to process variants using more columns. In this study, the MCSGP process was experimentally characterized specifically with respect to its unique degrees of freedom, i.e. Read More

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http://dx.doi.org/10.1002/biot.201800732DOI Listing

Coculture of Endothelial Cells with Human Pluripotent Stem Cell-Derived Cardiac Progenitors Reveals a Differentiation Stage-Specific Enhancement of Cardiomyocyte Maturation.

Biotechnol J 2019 Mar 30:e1800725. Epub 2019 Mar 30.

Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA.

Cardiomyocytes (CMs) generated from human pluripotent stem cells (hPSCs) are immature in their structure and function, limiting their potential in disease modeling, drug screening, and cardiac cellular therapies. Prior studies have demonstrated that coculture of hPSC-derived CMs with other cardiac cell types, including endothelial cells (ECs), can accelerate CM maturation. To address whether the CM differentiation stage at which ECs are introduced affects CM maturation, we cocultured hPSC-derived ECs with hPSC-derived cardiac progenitor cells (CPCs) and CMs, and analyzed molecular and functional attributes of maturation. Read More

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http://dx.doi.org/10.1002/biot.201800725DOI Listing

Development of a RecE/T-assisted CRISPR-Cas9 toolbox for Lactobacillus.

Biotechnol J 2019 Mar 30:e1800690. Epub 2019 Mar 30.

Jiangsu National Synergetic Innovation Center for Advanced Materials, SICAM, 200 North Zhongshan Road, Nanjing, China.

Lactobacilli are members of a large family involved in industrial food fermentation, therapeutics, and health promotion. However, the development of genetic manipulation tools for this genus lags behind its relative industrial and medical significance. The development of CRISPR-based genome engineering for Lactobacillus is now underway. Read More

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http://dx.doi.org/10.1002/biot.201800690DOI Listing

Biotechnology, Big Data and Artificial Intelligence.

Biotechnol J 2019 Mar 30:e1800613. Epub 2019 Mar 30.

INESC-ID, Instituto Superior Técnico, University of Lisbon, Portugal.

Developments in biotechnology are increasingly dependent on the extensive use of big data, generated by modern high-throughput instrumentation technologies and stored in thousands of databases, public and private. Future developments in this area depend, critically, on the ability of biotechnology researchers to master the skills required to effectively integrate their own contributions with the large amounts of information available in these databases. This article offers a perspective of the relations that exist between the fields of big data and biotechnology, including the related technologies of artificial intelligence and machine learning, and describes how data integration, data exploitation and process optimization correspond to three essential steps in any future biotechnology project. Read More

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http://dx.doi.org/10.1002/biot.201800613DOI Listing
March 2019
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Systems Metabolic Engineering Meets Machine Learning: A new era for data-driven metabolic engineering.

Biotechnol J 2019 Mar 30:e1800416. Epub 2019 Mar 30.

McKetta Department of Chemical Engineering, The University of Texas at Austin, Austin, Texas, USA.

The recent increase in high-throughput capacity of 'omics datasets combined with advances and interest in machine learning have created great opportunities for systems metabolic engineering. In this regard, data-driven modeling methods have become increasingly valuable to metabolic strain design. In this review we discuss the nature of 'omics and provide a broad introduction to the machine learning algorithms combining these datasets into predictive models of metabolism and metabolic rewiring. Read More

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http://dx.doi.org/10.1002/biot.201800416DOI Listing

Synthetic Biology Toolkits for Metabolic Engineering of Cyanobacteria.

Biotechnol J 2019 Mar 30:e1800496. Epub 2019 Mar 30.

Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore, Singapore.

Cyanobacteria are of great importance to Earth's ecology. Due to their capability in photosynthesis and C1 metabolism, they are ideal microbial chassis that can be engineered for direct conversion of carbon dioxide and solar energy to biofuels and biochemicals. Facilitated by the elucidation of basic biology of the photoautotrophic microbes and rapid advances in synthetic biology, genetic toolkits have been developed to enable implementation of non-natural functionalities in engineered cyanobacteria. Read More

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http://dx.doi.org/10.1002/biot.201800496DOI Listing

Next Generation Industrial Biotechnology-Transforming the Current Industrial Biotechnology into Competitive Processes.

Biotechnol J 2019 Mar 30:e1800437. Epub 2019 Mar 30.

MOE Lab of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, China.

Chemical industry has made contribution to modern society, providing cost competitive products for our daily usages. However, it now faces a serious challenge regarding environmental pollutions and greenhouse gas emission. With the rapid development of molecular biology, biochemistry and synthetic biology, industrial biotechnology has evolved to become more efficient for production of chemicals and materials. Read More

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http://dx.doi.org/10.1002/biot.201800437DOI Listing

Broadening the Scope of Enforced ATP Wasting as a Tool for Metabolic Engineering in Escherichia coli.

Biotechnol J 2019 Mar 30:e1800438. Epub 2019 Mar 30.

Analysis and Redesign of Biological Networks, Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany.

The targeted increase of cellular ATP turnover (enforced ATP wasting) has recently been recognized as a promising tool for metabolic engineering when product synthesis is coupled with net ATP formation. The goal of the present study was to further examine and to further develop the concept of enforced ATP wasting and to broaden its scope for potential applications. In particular, considering the fermentation products synthesized by E. Read More

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http://dx.doi.org/10.1002/biot.201800438DOI Listing

Evolutionary engineering of Corynebacterium glutamicum.

Biotechnol J 2019 Mar 30:e1800444. Epub 2019 Mar 30.

Institute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich, Jülich, Germany.

A unique feature of biotechnology is that we can harness the power of evolution to improve process performance. Rational engineering of microbial strains has led to the establishment of a variety of successful bioprocesses, but is hampered by the overwhelming complexity of biological systems. Evolutionary engineering represents a straightforward approach for fitness-linked phenotypes (e. Read More

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http://dx.doi.org/10.1002/biot.201800444DOI Listing

In silico Metabolic Design of Two-strain Biofilm Systems Predicts Enhanced Biomass Production and Biochemical Synthesis.

Biotechnol J 2019 Mar 30:e1800511. Epub 2019 Mar 30.

Department of Chemical Engineering and Institute for Applied Life Sciences, University of Massachusetts, Amherst, Massachusetts, USA.

Engineered biofilm consortia have the potential to solve important biotechnological problems that have proved difficult for monoculture biofilms and planktonic consortia such as conversion of lignocellulosic material to useful biochemicals. While considerable experimental progress has been reported for engineering and characterizing biofilm consortia, the field still lacks in silico tools for simulation, design and optimization of stable, robust and productive designed consortia. We developed biofilm consortia metabolic models for two coculture systems centered around the ecological design motif of a primary cell type that utilizes a supplied electron donor and secretes acetate as a byproduct and a secondary cell type that consumes the acetate relieving byproduct inhibition on the primary cell type and enhancing overall system biomass. Read More

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http://dx.doi.org/10.1002/biot.201800511DOI Listing

Efficient human genome editing using SaCas9 ribonucleoprotein complexes.

Biotechnol J 2019 Mar 30:e1800689. Epub 2019 Mar 30.

School of Ophthalmology and Optometry, Eye Hospital, State Key Laboratory of Ophthalmology, Optometry and Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, China.

Genome editing using RNA-guided nucleases in their ribonucleoprotein (RNP) form represents a promising strategy for gene modification and therapy because they are free of exogenous DNA integration and have reduced toxicity in vivo and ex vivo. However, genome editing by Cas9 nuclease from Staphylococcus aureus (SaCas9), has not been reported in its RNP form, which recognizes a longer protospacer adjacent motif (PAM), 5'-NNGRRT-3', compared with SpCas9(Streptococcus pyogenes Cas9) of 5'-NGG-3' PAM. Here, we report SaCas9-RNP mediated genome editing in human cells. Read More

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http://dx.doi.org/10.1002/biot.201800689DOI Listing
March 2019
1 Read

Newly Identified HNP-F from Human Neutrophil Peptide 1 Promotes Hemostasis.

Biotechnol J 2019 Mar 30:e1800606. Epub 2019 Mar 30.

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

Active hemostatic agents can play a crucial role in saving patients' lives during surgery. Active hemostats have several advantages including utilization of natural blood coagulation and biocompatibility. Among them, although HNP-1 was previously reported with the hemostatic mechanism, which part of HNP-1 was not known that facilitates the hemostatic activity. Read More

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http://dx.doi.org/10.1002/biot.201800606DOI Listing
March 2019
2 Reads

Production of 3-fucosyllactose in engineered Escherichia coli with α-1,3-fucosyltransferase from Helicobacter pylori.

Biotechnol J 2019 Mar 30:e1800498. Epub 2019 Mar 30.

Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.

3-Fucosyllactose (3-FL), one of the major oligosaccharides in human breast milk, was produced in engineered Escherichia coli. In order to search for a good α-1,3-fucosyltransferase, three bacterial α-1,3-fucosyltransferases were expressed in engineered E. coli deficient in β-galactosidase activity and expressing the essential enzymes for production of GDP-l-fucose, the donor of fucose for 3-FL biosynthesis. Read More

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http://dx.doi.org/10.1002/biot.201800498DOI Listing

Enhanced Saccharification and Fermentation of Rice Straw by Reducing the Concentration of Phenolic Compounds Using an Immobilized Enzyme Cocktail.

Biotechnol J 2019 Mar 30:e1800468. Epub 2019 Mar 30.

Key Laboratory of Biopesticide and Chemical Biology, Ministry of Education, College of Life Sciences, Gutian Edible Fungi Research Institute, Fujian Agriculture and Forestry University, Fuzhou, Fujian province, PR China.

The production of bioethanol from rice straw can contribute to the rural economy and provide clean fuel in a sustainable manner. However, phenolic compounds, which are mostly produced during acid pretreatment of biomass, act as inhibitors of fermenting microorganisms. Laccase is well known for its ability to oxidize lignin and phenolic compounds derived from lignocellulosic biomass. Read More

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http://dx.doi.org/10.1002/biot.201800468DOI Listing

Screening of commercial enzymes for transfructosylation of tyrosol: Effect of process conditions and reaction network.

Biotechnol J 2019 Mar 30:e1800571. Epub 2019 Mar 30.

Department of Chemical and Biochemical Engineering, Institute of Chemical and Environmental Engineering, Faculty of Chemical and Food Technology, Slovak University of Technology, Bratislava, Slovakia.

Enzymatic fructosylation of organic acceptors other than saccharides brings new possibilities to synthesize molecules that do not exist in nature. The introduction of fructosyl moiety may lead to glycosides possessing enhanced physico-chemical and bioactive properties which could be useful in the pharmaceutical and cosmetic industry. In this work, the regioselective synthesis of tyrosol β-D-fructofuranoside catalyzed by β-fructofuranosidase is investigated. Read More

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http://dx.doi.org/10.1002/biot.201800571DOI Listing

Yeast Systems Biology: Model organism and Cell Factory.

Authors:
Jens Nielsen

Biotechnol J 2019 Mar 29:e1800421. Epub 2019 Mar 29.

BioInnovation Institute, Ole Måløes Vej 3, Copenhagen N, Denmark.

For thousands of years the yeast Saccharomyces cerevisiae has served as a cell factory for the production of bread, beer, and wine. In more recent years, this yeast has also served as a cell factory for producing many different fuels, chemicals, food ingredients and pharmaceuticals. S. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/biot.2018004
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http://dx.doi.org/10.1002/biot.201800421DOI Listing
March 2019
1 Read

Oil palm biomass biorefinery for sustainable production of renewable materials.

Biotechnol J 2019 Mar 29:e1800394. Epub 2019 Mar 29.

Section of Bioengineering Technology, Universiti Kuala Lumpur, Malaysian Institute of Chemical and Bioengineering Technology, Alor Gajah, Malaysia.

Oil palm biomass is widely known for its potential as a renewable resource for various value-added products due to its lignocellulosic content and availability. Oil palm biomass biorefinery is a certain homerun money-making industry that comes with socio-political benefits through job opportunities created as well as a great environmental conservation initiative. Many studies have been conducted on the technological advancements of oil-palm biomass-derived renewable materials, which are discussed comprehensively in this review. Read More

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http://dx.doi.org/10.1002/biot.201800394DOI Listing
March 2019
3.708 Impact Factor

Application of Imaging Flow Cytometry for the Characterization of Intracellular Attributes in Chinese Hamster Ovary Cell Lines at the Single Cell Level.

Biotechnol J 2019 Mar 29:e1800675. Epub 2019 Mar 29.

MedImmune, Granta Park, Cambridge, UK.

Biopharmaceutical manufacturing using Chinese hamster ovary (CHO) cells requires the generation of high-producing clonal cell lines. During cell line development, cell cloning using fluorescence activated cell sorting (FACS) has the potential to combine isolation of single cells with sorting based on specific cellular attributes that correlate with productivity and/or growth, identifying cell lines with desirable phenotypes for manufacturing. This study describes the application of imaging flow cytometry (IFC) to characterize recombinant cell lines at the single cell level to identify cell attributes predictive of productivity. Read More

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http://dx.doi.org/10.1002/biot.201800675DOI Listing

Engineering of phosphoserine aminotransferase increases the conversion of L-homoserine to 4-hydroxy-2-ketobutyrate in a glycerol-independent pathway of 1,3-propanediol production from glucose.

Biotechnol J 2019 Mar 29:e1900003. Epub 2019 Mar 29.

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

Phosphoserine aminotransferase (SerC) from Escherichia coli MG1655 was engineered to catalyze the deamination of homoserine to 4-hydroxy-2-ketobutyrate, a key reaction in producing 1,3-propanediol (1,3-PDO) from glucose in a novel glycerol-independent metabolic pathway. To this end, a computation-based rational approach was used to change the substrate specificity of SerC from L-phosphoserine to L-homoserine. In this approach, molecular dynamics simulations and virtual screening were combined to predict mutation sites. Read More

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http://dx.doi.org/10.1002/biot.201900003DOI Listing

Pathway engineering of Bacillus subtilis for enhanced N-acetylneuraminic acid production via whole-cell biocatalysis.

Biotechnol J 2019 Mar 29:e1800682. Epub 2019 Mar 29.

Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi, China.

N-acetylneuraminic acid (NeuAc) is a common sialic acid that has wide-ranging applications as nutraceuticals and pharmaceuticals. However, low production efficiency and high environmental pollution of traditional extraction and chemical synthesis methods constrain NeuAc supply. Here, we developed a biological approach for food-grade NeuAc production via whole-cell biocatalysis by generally regarded as safe (GRAS) bacterium Bacillus subtilis. Read More

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http://dx.doi.org/10.1002/biot.201800682DOI Listing

Systems Metabolic Engineering Strategies for Non-Natural Microbial Polyester Production.

Biotechnol J 2019 Mar 9:e1800426. Epub 2019 Mar 9.

Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Plus Program), Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea.

Plastics, used everyday, are mostly synthetic polymers derived from fossil resources, and their accumulation is becoming a serious concern worldwide. Polyhydroxyalkanoates (PHAs) are naturally produced polyesters synthesized and intracellularly accumulated by many different microorganisms. PHAs are good alternatives to petroleum-based plastics because they possess a wide range of material properties depending on monomer types and molecular weights. Read More

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http://dx.doi.org/10.1002/biot.201800426DOI Listing

Continuous solvent/detergent virus inactivation using a packed-bed reactor.

Biotechnol J 2019 Feb 27:e1800646. Epub 2019 Feb 27.

Austria Centre for Industrial Biotechnology, Vienna, Austria.

Continuous virus inactivation remains one of the missing pieces while the biopharma industry moves toward continuous manufacturing. The challenges of adapting virus inactivation (VI) to continuous operation are two-fold: (1) achieving fluid homogeneity and (2) a narrow residence time distribution (RTD) for fluid incubation. To address these challenges, we implemented a dynamic active in-line mixer and a packed-bed continuous virus inactivation reactor (CVIR), which acts as a narrow RTD incubation chamber. Read More

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http://dx.doi.org/10.1002/biot.201800646DOI Listing
February 2019
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Polymerization of Horseradish Peroxidase by a Laccase-Catalyzed Tyrosine Coupling Reaction.

Biotechnol J 2019 Feb 27:e1800531. Epub 2019 Feb 27.

Department of Applied Chemistry, Graduate School of Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan.

The polymerization of proteins can create newly active and large bio-macromolecular assemblies that exhibit unique functionalities depending on the properties of the building block proteins and the protein units in polymers. Herein, the first enzymatic polymerization of horseradish peroxidase (HRP) is reported. Recombinant HRPs fused with a tyrosine-tag (Y-tag) through a flexible linker at the N- and/or C-termini are expressed in silkworm, Bombyx mori. Read More

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http://dx.doi.org/10.1002/biot.201800531DOI Listing
February 2019

Cross interaction chromatography based QSAR model for early stage screening to facilitate enhanced developability of monoclonal antibody therapeutics.

Biotechnol J 2019 Feb 27:e201800696. Epub 2019 Feb 27.

School of Engineering, Newcastle University, Newcastle upon Tyne, UK.

Monoclonal antibodies (mAbs) constitute a significant and rapidly growing sector of the biopharmaceutical industry. However, their growth is impeded by developability issues such as polyspecificity and lack of solubility which leads to attrition as well as manufacturing failures. In this study a multi-tool hybrid QSAR model development framework is described. Read More

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http://dx.doi.org/10.1002/biot.201800696DOI Listing
February 2019

Enhanced phenyllactic acid production in Escherichia coli via oxygen limitation and shikimate pathway gene expression.

Biotechnol J 2019 Feb 27:e1800478. Epub 2019 Feb 27.

Graduate School of Science, Technology and Innovation, Kobe University, Kobe, Japan.

3-Phenyllactic acid (PhLA) is useful as a start-up material in the pharmaceutical and biorefinery industries. To enhance the production of PhLA from glucose using recombinant Escherichia coli, the effects of glucose concentration and oxygen limitation on PhLA production were assessed in a fed-batch system using a dissolved oxygen (DO)-stat method. The highest titer of PhLA (7. Read More

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http://dx.doi.org/10.1002/biot.201800478DOI Listing
February 2019

Tandem Cell-Free Protein Synthesis as a Tool for Rapid Screening of Optimal Molecular Chaperones.

Biotechnol J 2019 Feb 27:e1800523. Epub 2019 Feb 27.

Department of Chemical Engineering and Applied Chemistry, Chungnam National University, 99 Daehak-ro, 34134, Daejeon, Korea.

A simple and flexible method is developed for rapid screening of molecular chaperones that enhance the functional expression of recombinant proteins. A panel of molecular chaperones are transiently expressed in a reaction mixture of cell-free protein synthesis and then a target protein is subsequently expressed in the presence of these presynthesized molecular chaperones. The biological activity of the cell-free synthesized target protein is compared to identify the effective molecular chaperones. Read More

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http://dx.doi.org/10.1002/biot.201800523DOI Listing
February 2019

Supramolecular Polymeric Hydrogels for Ultrasound-Guided Protein Release.

Biotechnol J 2019 Feb 27:e1800530. Epub 2019 Feb 27.

Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo, 153-8904, Japan.

An ultrasound-responsive carrier for protein drugs is promising for site-specific release of proteins at disease sites in a designated time course because ultrasound readily penetrates deep into the interior of the body in a non-invasive way. However, the guideline for designing ultrasound-responsive carriers that are applicable to any protein remains to be established. Here, the aim is to develop an ultrasound-responsive material for the controlled release of a variety of proteins regardless of their charge and structure. Read More

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http://dx.doi.org/10.1002/biot.201800530DOI Listing
February 2019

Steps Toward High-Performance PLA: Economical Production of d-Lactate Enabled by a Newly Isolated Sporolactobacillus terrae Strain.

Biotechnol J 2019 Feb 27:e1800656. Epub 2019 Feb 27.

State Key Laboratory of Microbial Metabolism Joint International Research Laboratory of Metabolic and Developmental Sciences and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai,, P. R. China.

Optically pure d-lactate production has received much attention for its critical role in high-performance polylactic acid production. However, the current technology can hardly meet the comprehensive demand of industrialization on final titer, productivity, optical purity, and raw material costs. Here, an efficient d-lactate producer strain, Sporolactobacillus terrae (S. Read More

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http://dx.doi.org/10.1002/biot.201800656DOI Listing
February 2019
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High-Affinity Antibody Detection with a Bivalent Circularized Peptide Containing Antibody-Binding Domains.

Biotechnol J 2019 Feb 27:e1800647. Epub 2019 Feb 27.

Department of Chemical and Biological Engineering, University at Buffalo, Buffalo, NY, 14260, USA.

Direct chemical labeling of antibody produces molecules with poorly defined modifications. Use of a small antibody-binding protein as an adapter can simplify antibody functionalization by forming a specific antibody-bound complex and introducing site-specific modifications. To stabilize a noncovalent antibody complex that may be used without chemical crosslinking, a bivalent antibody-binding protein is engineered with an improved affinity of interaction by joining two Z domains with a conformationally flexible linker. Read More

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http://dx.doi.org/10.1002/biot.201800647DOI Listing
February 2019

Gene-centric metagenome analysis reveals gene clusters for carbon monoxide conversion and validates isolation of a clostridial acetogen for C2 chemical production.

Biotechnol J 2019 Feb 25:e1800471. Epub 2019 Feb 25.

School of Earth Sciences and Environmental Engineering, Gwangju Institute of Science and Technology (GIST), 123 Cheomdangwagi-ro, Buk-gu, Korea.

Synthetic gas (syngas) fermentation is largely dependent on acetogens that occur in various anaerobic environmental samples including soil, sediment, and feces. Here we report the metagenomic isolation of acetogens for C2 chemical production from syngas. Screening acetogens for C2 chemical production typically involves detecting the presence of the Wood-Ljungdahl Pathway (WLP) for carbon monoxide (CO) conversion. Read More

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http://dx.doi.org/10.1002/biot.201800471DOI Listing
February 2019

CRISPR/Cas9-Mediated Knockout of MicroRNA-744 Improves Antibody Titer of CHO Production Cell Lines.

Biotechnol J 2019 Feb 25:e1800477. Epub 2019 Feb 25.

Institute of Applied Biotechnology, University of Applied Sciences Biberach, Hubertus-Liebrecht-Str. 35, Biberach, 88400, Germany.

MicroRNAs (miRNAs) are noncoding RNAs that serve as versatile molecular engineering tools to improve production cells by overexpression or knockdown of miRNAs showing beneficial or adverse effects on cell-culture performance. The genomic knockout (KO) of noncoding RNAs in Chinese hamster ovary (CHO) production cells has not been reported. However, given the significant number of miRNAs showing negative effects on CHO-bioprocess performance and the development of clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins (CRISPR/Cas9), genome editing tools facilitate precise optimization of CHO cells via modulation of noncoding RNAs. Read More

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http://dx.doi.org/10.1002/biot.201800477DOI Listing
February 2019

Implementation of a fully automated microbial cultivation platform for strain and process screening.

Biotechnol J 2019 Feb 22:e201800625. Epub 2019 Feb 22.

Boehringer Ingelheim RCV GmbH & Co KG, Dr. Boehringer-Gasse 5-11, Vienna, Austria.

Advances in molecular biotechnology have resulted in the generation of numerous potential production strains. Because every strain can be screened under various process conditions, the number of potential cultivations is multiplied. To exploit this potential without increasing the associated timelines requires a cultivation platform that offers increased throughput and flexibility to perform various bioprocess screening protocols. Read More

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http://dx.doi.org/10.1002/biot.201800625DOI Listing
February 2019
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Enhanced CHO clone screening: Applying Targeted Locus Amplification and Next-Generation Sequencing technologies during cell line development.

Biotechnol J 2019 Feb 22:e201800371. Epub 2019 Feb 22.

Novartis Institutes for BioMedical Research, Integrated Biologics Profiling Unit, Basel, Switzerland.

Early analytical clone screening is important during CHO cell line development of biotherapeutic antibodies to select clones with most favorable stability and product quality. The term clone describes CHO cells derived from a single cell (clonally-derived cell line). While sensitive sequence confirmation methods using mass spectrometry have limitations in throughput and turnaround time, next-generation sequencing (NGS) technologies have emerged as alternatives for clone analytics. Read More

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http://dx.doi.org/10.1002/biot.201800371DOI Listing
February 2019
3.708 Impact Factor

Construction of a Model Culture System of Human Colonic Microbiota to Detect Decreased Lachnospiraceae Abundance and Butyrogenesis in the Feces of Ulcerative Colitis Patients.

Biotechnol J 2019 Feb 21:e1800555. Epub 2019 Feb 21.

Department of Bioresource Science, Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, Hyogo, 657-8501, Japan.

Compositional alteration of the gut microbiota is associated with ulcerative colitis (UC). Here, a model culture system is established for the in vitro human colonic microbiota of UC, which will be helpful for determining medical interventions. 16S ribosomal RNA sequencing confirms that UC models are successfully developed from fecal inoculum and retain the bacterial species biodiversity of UC feces. Read More

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http://dx.doi.org/10.1002/biot.201800555DOI Listing
February 2019
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Rewiring the Central Metabolic Pathway for High-Yield L-Serine Production in Corynebacterium Glutamicum by Using Glucose.

Biotechnol J 2019 Feb 21:e1800497. Epub 2019 Feb 21.

National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi, China.

L-serine is widely used in the pharmaceutical, food and cosmetic industries. The direct fermentative production of L-serine from glucose in Corynebacterium glutamicum has been achieved, but the yield is generally low. In this study, we rewired the central metabolic pathway to direct higher accumulation of glycerate-3-phosphate (3-PG), the precursor for L-serine biosynthesis, thereby freeing up more carbon to enhance L-serine production and yield. Read More

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http://dx.doi.org/10.1002/biot.201800497DOI Listing
February 2019

Mass Balance Model with Donnan Equilibrium Accurately Describes Unusual pH and Excipient Profiles during Diafiltration of Monoclonal Antibodies.

Biotechnol J 2019 Feb 21:e1800517. Epub 2019 Feb 21.

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

There is extensive experimental data showing that the final pH and buffer composition after protein diafiltration, particularly with monoclonal antibodies, can be considerably different than that in the diafiltration buffer due to electrostatic interactions between the charged protein and the charged ions. Previous models for this behavior have focused on the final (equilibrium) partitioning and are unable to explain the complex pH and concentration profiles during the diafiltration process. The objective of this study was to develop a new model for antibody diafiltration based on solution of the transient mass balance equations, with the permeate concentrations of the charged species evaluated assuming Donnan equilibrium across the semipermeable membrane in combination with electroneutrality constraints. Read More

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http://dx.doi.org/10.1002/biot.201800517DOI Listing
February 2019

Dimerization of Proline Dehydrogenase from Thermus thermophilus Is Crucial for Its Thermostability.

Biotechnol J 2019 Feb 21:e1800540. Epub 2019 Feb 21.

Laboratory of Biochemistry, Wageningen University & Research, Stippeneng 4, 6708 WE Wageningen, The Netherlands.

Thermus thermophilus proline dehydrogenase ( TtProDH) catalyzes the first step in proline catabolism. The thermostable flavoenzyme consists of a distorted triosephosphate isomerase (TIM) barrel and three N-terminal helices: αA, αB, and αC. Using maltose-binding protein (MBP) fused constructs, it has been recently demonstrated that helix αC is crucial for TtProDH catalysis and for tetramerization through positioning of helix α8. Read More

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http://dx.doi.org/10.1002/biot.201800540DOI Listing
February 2019