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    12449 results match your criteria Biotechnology and Bioengineering [Journal]

    1 OF 249

    Developing a Cas9-based tool to engineer native plasmids in Synechocystis sp. PCC 6803.
    Biotechnol Bioeng 2018 Jun 13. Epub 2018 Jun 13.
    Department of Energy, Environmental and Chemical Engineering, Washington University in St. Louis, Saint Louis, MO, USA.
    The oxygenic photosynthetic bacterium Synechocystis sp. PCC 6803 (S6803) is a model cyanobacterium widely used for fundamental research and biotechnology applications. Due to its polyploidy, existing methods for genome engineering of S6803 require multiple rounds of selection to modify all genome copies, which is time-consuming and inefficient. Read More

    Mechanical load increase-induced changes in cytoskeletal structure and cellular barrier function in human cerebral endothelial cells.
    Biotechnol Bioeng 2018 Jun 13. Epub 2018 Jun 13.
    Department of Biological Engineering, Inha University, Incheon, Korea.
    Globally, approximately billion patients are estimated to suffer from neurological disorders. Although there are many therapeutic candidates for the central nervous system (CNS), treatment of brain disorders is restricted by the blood-brain barrier (BBB), which is a highly selective membrane that protects the brain from exogenous substances. This study was undertaken to develop a novel strategy to overcome the BBB and improve the efficiency of drug delivery to the brain by mechanical load increase using hypergravity. Read More

    Mechanisms of precipitate formation during the purification of an Fc-fusion protein.
    Biotechnol Bioeng 2018 Jun 13. Epub 2018 Jun 13.
    Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE, USA.
    Protein precipitates that arise during bioprocessing can cause manufacturing challenges but they can also aid in clearance of host-cell protein and DNA impurities. Such precipitates differ from many protein precipitates that have been studied previously in their heterogeneous composition, particularly in the presence of high concentrations of the product protein. Here we characterize the precipitates that form after neutralization of Protein A purified and viral-inactivated material of an Fc-fusion protein produced in Chinese hamster ovary (CHO) cells. Read More

    Low-pH production of D-lactic acid using newly isolated acid tolerant yeast Pichia kudriavzevii NG7.
    Biotechnol Bioeng 2018 Jun 13. Epub 2018 Jun 13.
    Cell Factory Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, Republic of Korea.
    Lactic acid is a platform chemical for the sustainable production of various materials. To develop a robust yeast platform for low-pH production of D-lactic acid, an acid-tolerant yeast strain was isolated from grape skins and named Pichia kudriavzevii NG7 by ribosomal RNA sequencing. This strain was able to grow at pH 2. Read More

    Modular pathway engineering of key carbon-precursor supply-pathways for improved N-acetylneuraminic acid production in Bacillus subtilis.
    Biotechnol Bioeng 2018 Jun 13. Epub 2018 Jun 13.
    Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, Wuxi, China.
    N-acetylneuraminic acid (NeuAc) is widely used as a nutraceutical for facilitating infant brain development, maintaining brain health, and enhancing immunity. Currently, NeuAc is mainly produced by extraction from egg yolk and milk, or via chemical synthesis. However, its low concentration in natural resources and its non-ecofriendly chemical synthesis results in insufficient NeuAc production and environmental pollution, respectively. Read More

    A mathematical model of intracellular behavior of microalgae for predicting growth and intracellular components syntheses under nutrient replete and deplete conditions.
    Biotechnol Bioeng 2018 Jun 13. Epub 2018 Jun 13.
    Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Deajeon, Republic of Korea.
    Microalgae is a promising biomass source for renewable fuels and chemicals production. To describe microalgal behavior and improve their cultivation, various kinetic models have been proposed. However, previous works have focused on biomass formation and lipids production only, even though carbohydrates and proteins are also important products, not only for understanding the metabolic behavior of microalgae but also for enhancing the economic viability through value-added side products. Read More

    Rational Design of Thiolase Substrate Specificity for Metabolic Engineering Applications.
    Biotechnol Bioeng 2018 Jun 7. Epub 2018 Jun 7.
    Microbiology Graduate Program, Massachusetts Institute of Technology, Cambridge, MA.
    Metabolic engineering efforts require enzymes that are both highly active and specific towards the synthesis of a desired output product in order to be commercially feasible. The 3-hydroxyacid pathway (3HA), also known as the reverse β-oxidation (r-BOX) or coenzyme-A dependent chain elongation pathway, can allow for the synthesis of dozens of useful compounds of various chain lengths and functionalities. However, this pathway suffers from byproduct formation, which lowers yields of the desired longer chain products, as well as increases downstream separation costs. Read More

    Reconstruction of 24 Penicillium genome-scale metabolic models shows diversity based on their secondary metabolism.
    Biotechnol Bioeng 2018 Jun 5. Epub 2018 Jun 5.
    Chalmers University of Technology, Department of Biology and Biological Engineering, Division of Systems and Synthetic Biology, Gothenburg, Sweden.
    Modelling of metabolism at the genome-scale have proved to be an efficient method for explaining observed phenotypic traits in living organisms. Further, it can be used as a means of predicting the effect of genetic modifications e.g. Read More

    Live imaging flow bioreactor for the simulation of articular cartilage regeneration after treatment with bioactive hydrogel.
    Biotechnol Bioeng 2018 Jun 5. Epub 2018 Jun 5.
    The Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
    Osteochondral defects (OCDs) are conditions affecting both cartilage and the underlying bone. Since cartilage is not spontaneously regenerated, our group has recently developed a strategy of injecting bioactive alginate hydrogel into the defect for promoting endogenous regeneration of cartilage via presentation of affinity-bound transforming growth factor β1 (TGF-β1). As in vivo model systems often provide only limited insights regarding the mechanism behind regeneration processes, here we describe a novel flow bioreactor for the in vitro modeling of the OCD microenvironment, designed to promote cell recruitment from the simulated bone marrow compartment into the hydrogel, under physiological flow conditions. Read More

    Broadened glycosylation patterning of heterologously produced erythromycin.
    Biotechnol Bioeng 2018 Jun 5. Epub 2018 Jun 5.
    Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, New York, USA.
    The biosynthetic flexibility associated with the antibiotic natural product erythromycin is both remarkable and utilitarian. Product formation is marked by a modular nature where directing compound variation increasingly spans both the secondary metabolite core scaffold and adorning functionalization patterns. The resulting molecular diversity allows for chemical expansion of the native compound structural space. Read More

    Metabolic engineering of Saccharomyces cerevisiae for production of fatty acid-derived hydrocarbons.
    Biotechnol Bioeng 2018 Jun 5. Epub 2018 Jun 5.
    Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing, China.
    Fatty acid derived hydrocarbons attract increasing attention as biofuels due to their immiscibility with water, high energy content, low freezing point, and high compatibility with existing refineries and end-user infrastructures. Yeast Saccharomyces cerevisiae has advantages for production of fatty acid derived hydrocarbons as its native routes towards fatty acid synthesis involve only a few reactions that allow more efficient conversion of carbon substrates. Here we describe major biosynthetic pathways of fatty acid derived hydrocarbons in yeast, and summarize key metabolic engineering strategies, including enhancing precursor supply, eliminating competing pathways, and expressing heterologous pathways. Read More

    Milligram scale production of potent recombinant small interfering RNAs in Escherichia coli.
    Biotechnol Bioeng 2018 Jun 5. Epub 2018 Jun 5.
    Department of Biomedical Sciences, College of Veterinary Medicine and Life Sciences, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon Tong, Kowloon, Hong Kong.
    Small interfering RNAs (siRNAs) are invaluable research tools for studying gene functions in mammalian cells. siRNAs are mainly produced by chemical synthesis or by enzymatic digestion of dsRNAs produced in vitro. Recently bacterial cells, engineered with ectopic plant viral siRNA binding protein p19, have enabled the production of 'recombinant' siRNAs (pro-siRNAs). Read More

    Evaluation of encapsulating and microporous non-degradable hydrogel scaffold designs on islet engraftment in rodent models of diabetes.
    Biotechnol Bioeng 2018 Jun 5. Epub 2018 Jun 5.
    Department of Biomedical Engineering, University of Michigan, 1119 Carl A. Gerstacker Building, 2200 Bonisteel Boulevard, Ann Arbor, MI.
    Islet transplantation is a promising therapeutic option for Type 1 diabetes mellitus, yet the current delivery into the hepatic portal vasculature is limited by poor engraftment. Biomaterials have been employed as a means to promote engraftment and function at extrahepatic sites, with strategies being categorized as encapsulation or microporous scaffolds that can either isolate or integrate islets with the host tissue, respectively. While these approaches are typically studied separately using distinct material platforms, herein, we developed non-degradable polyethylene glycol (PEG)-based hydrogels for islet encapsulation or as microporous scaffolds for islet seeding in order to compare the initial engraftment and function of islets in syngeneic diabetic mice. Read More

    Microdevice-based solid-phase polymerase chain reaction for rapid detection of pathogenic microorganisms.
    Biotechnol Bioeng 2018 May 19. Epub 2018 May 19.
    Department of BioNano Technology, Gachon University, Seongnam-si, Gyeonggi-do, Republic of Korea.
    We demonstrate the integration of DNA amplification and detection functionalities developed on a lab-on-a-chip microdevice utilizing solid-phase polymerase chain reaction (SP-PCR) for point-of-need (PON) DNA analyses. First, the polycarbonate microdevice was fabricated by thermal bonding  to contain microchambers as reservoirs for performing SP-PCR. Next, the microchambers were subsequently modified with polyethyleneimine and glutaraldehyde for immobilizing amine-modified forward primers. Read More

    Morphological analysis of pore size and connectivity in a thick mixed-culture biofilm.
    Biotechnol Bioeng 2018 May 19. Epub 2018 May 19.
    Department of Civil and Environmental Engineering, Northwestern University, Evanston, Illinois.
    Morphological parameters are commonly used to predict transport and metabolic kinetics in biofilms. Yet, quantification of biofilm morphology remains challenging because of imaging technology limitations and lack of robust analytical approaches. We present a novel set of imaging and image analysis techniques to estimate internal porosity, pore size distributions, and pore network connectivity to a depth of 1 mm at a resolution of 10 µm in a biofilm exhibiting both heterotrophic and nitrifying activities. Read More

    Degradation of recombinant proteins by CHO host cell proteases is prevented by Matriptase-1 knock-out.
    Biotechnol Bioeng 2018 May 19. Epub 2018 May 19.
    Novartis Institutes for Biomedical Research, Basel, Switzerland.
    An increasing number of non-antibody format proteins are entering the clinical development. However, one of the major hurdles for the production of non-antibody glycoproteins is host cell-related proteolytic degradation, which can drastically impact developability and timelines of pipeline projects. Chinese hamster ovary (CHO) cells are the preferred production host for recombinant therapeutic proteins. Read More

    Early identification of unusually clustered mutations and root causes in therapeutic antibody development.
    Biotechnol Bioeng 2018 May 19. Epub 2018 May 19.
    Product Development, Global Product Development and Supply, Bristol-Myers Squibb Company, Devens, Massachusetts.
    This study reports findings of an unusual cluster of mutations spanning 22 bp (base pairs) in a monoclonal antibody expression vector. It was identified by two orthogonal methods: mass spectrometry on expressed protein and next-generation sequencing (NGS) on the plasmid DNA. While the initial NGS analysis confirmed the designed sequence modification, intact mass analysis detected an additional mass of the antibody molecule expressed in CHO cells. Read More

    Bioengineering triacetic acid lactone production in Yarrowia lipolytica for pogostone synthesis.
    Biotechnol Bioeng 2018 May 19. Epub 2018 May 19.
    Department of Biological Chemistry, University of California, Irvine, California.
    Yarrowia lipolytica is an oleaginous yeast that is recognized for its ability to accumulate high levels of lipids, which can serve as precursors to biobased fuels and chemicals. Polyketides, such as triacetic acid lactone (TAL), can also serve as a precursor for diverse commodity chemicals. This study used Y. Read More

    Boosting mediated electron transfer in bioelectrochemical systems with tailored defined microbial cocultures.
    Biotechnol Bioeng 2018 May 19. Epub 2018 May 19.
    Institute of Applied Microbiology iAMB, Aachen Biology and Biotechnology ABBt, RWTH Aachen University, Aachen, Germany.
    Bioelectrochemical systems (BES) hold great promise for sustainable energy generation via a microbial catalyst from organic matter, for example, from wastewater. To improve current generation in BES, understanding the underlying microbiology of the electrode community is essential. Electron mediator producing microorganism like Pseudomonas aeruginosa play an essential role in efficient electricity generation in BES. Read More

    Low-adhesive ethylene vinyl alcohol-based packaging to xenogeneic islet encapsulation for type 1 diabetes treatment.
    Biotechnol Bioeng 2018 May 19. Epub 2018 May 19.
    Laboratory of Organ and Tissue Reconstruction, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
    Transplantation of encapsulated porcine islets is proposed to treat type 1 diabetes. However, the envelopment of fibrous tissue and the infiltration of immune cells impair islet function and eventually cause implant failure. It is known that hemodialysis using an ethylene vinyl alcohol (EVOH) membrane results in minor tissue responses. Read More

    Building a genome engineering toolbox in nonmodel prokaryotic microbes.
    Biotechnol Bioeng 2018 May 11. Epub 2018 May 11.
    National Renewable Energy Laboratory, Biosciences Center, Golden, CO.
    The realization of a sustainable bioeconomy requires our ability to understand and engineer complex design principles for the development of platform organisms capable of efficient conversion of cheap and sustainable feedstocks (e.g., sunlight, CO , and nonfood biomass) into biofuels and bioproducts at sufficient titers and costs. Read More

    Building a minimal and generalizable model of transcription factor-based biosensors: Showcasing flavonoids.
    Biotechnol Bioeng 2018 May 7. Epub 2018 May 7.
    Micalis Institute, INRA, AgroParisTech, University of Paris-Saclay, Jouy-en-Josas, France.
    Progress in synthetic biology tools has transformed the way we engineer living cells. Applications of circuit design have reached a new level, offering solutions for metabolic engineering challenges that include developing screening approaches for libraries of pathway variants. The use of transcription-factor-based biosensors for screening has shown promising results, but the quantitative relationship between the sensors and the sensed molecules still needs more rational understanding. Read More

    Combinatorial synthetic pathway fine-tuning and comparative transcriptomics for metabolic engineering of Raoultella ornithinolytica BF60 to efficiently synthesize 2,5-furandicarboxylic acid.
    Biotechnol Bioeng 2018 May 7. Epub 2018 May 7.
    Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi, China.
    The compound 5-hydroxymethylfurfural (HMF) has attracted much attention due to its versatility as an important bio-based platform chemical. Here, we engineered Raoultella ornithinolytica BF60 as a whole-cell biocatalyst for a highly efficient synthesis of 2,5-furandicarboxylic acid (FDCA) from HMF. Specifically, various expression cassettes of key genes, such as hmfH (gene encoding HMF/furfural oxidoreductase [HmfH]) and hmfo (gene encoding HMF oxidase), were designed and constructed for fine-tuning FDCA synthesis from HMF. Read More

    Non-Newtonian rheology in suspension cell cultures significantly impacts bioreactor shear stress quantification.
    Biotechnol Bioeng 2018 Apr 28. Epub 2018 Apr 28.
    Pharmaceutical Production Research Facility, Schulich School of Engineering, University of Calgary, Calgary, Alberta, Canada.
    The fields of regenerative medicine and tissue engineering require large-scale manufacturing of stem cells for both therapy and recombinant protein production, which is often achieved by culturing cells in stirred suspension bioreactors. The rheology of cell suspensions cultured in stirred suspension bioreactors is critical to cell growth and protein production, as elevated exposure to shear stress has been linked to changes in growth kinetics and genetic expression for many common cell types. Currently, little is understood on the rheology of cell suspensions cultured in stirred suspension bioreactors. Read More

    A reference genome of the Chinese hamster based on a hybrid assembly strategy.
    Biotechnol Bioeng 2018 Apr 28. Epub 2018 Apr 28.
    Delaware Biotechnology Institute, Newark, Delaware.
    Accurate and complete genome sequences are essential in biotechnology to facilitate genome-based cell engineering efforts. The current genome assemblies for Cricetulus griseus, the Chinese hamster, are fragmented and replete with gap sequences and misassemblies, consistent with most short-read-based assemblies. Here, we completely resequenced C. Read More

    Improving culture performance and antibody production in CHO cell culture processes by reducing the Warburg effect.
    Biotechnol Bioeng 2018 Apr 28. Epub 2018 Apr 28.
    Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, Queensland, Australia.
    Lactate is one of the key waste metabolites of mammalian cell culture. High lactate levels are caused by high aerobic glycolysis, also known as the Warburg effect, and are usually associated with adverse culture performance. Therefore, reducing lactate accumulation has been an ongoing challenge in the cell culture development to improve growth, productivity, and process robustness. Read More

    CRISPR interference-mediated metabolic engineering of Corynebacterium glutamicum for homo-butyrate production.
    Biotechnol Bioeng 2018 Apr 28. Epub 2018 Apr 28.
    Department of Food Science and Biotechnology, Sungkyunkwan University (SKKU), Suwon, Republic of Korea.
    Combinatorial metabolic engineering enabled the development of efficient microbial cell factories for modulating gene expression to produce desired products. Here, we report the combinatorial metabolic engineering of Corynebacterium glutamicum to produce butyrate by introducing a synthetic butyrate pathway including phosphotransferase and butyrate kinase reactions and repressing the essential acn gene-encoding aconitase, which has been targeted for downregulation in a genome-scale model. An all-in-one clustered regularly interspaced short palindromic repeats interference system for C. Read More

    Retrievable hydrogels for ovarian follicle transplantation and oocyte collection.
    Biotechnol Bioeng 2018 Apr 28. Epub 2018 Apr 28.
    Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.
    Cancer survivorship rates have drastically increased due to improved efficacy of oncologic treatments. Consequently, clinical concerns have shifted from solely focusing on survival to quality of life, with fertility preservation as an important consideration. Among fertility preservation strategies for female patients, ovarian tissue cryopreservation and subsequent reimplantation has been the only clinical option available to cancer survivors with cryopreserved tissue. Read More

    Accurate O delivery enabled benzene biodegradation through aerobic activation followed by denitrification-coupled mineralization.
    Biotechnol Bioeng 2018 Apr 28. Epub 2018 Apr 28.
    Biodesign Swette Center for Environmental Biotechnology, Arizona State University, Tempe, Arizona.
    Although benzene can be biodegraded when dissolved oxygen is sufficient, delivering oxygen is energy intensive and can lead to air stripping the benzene. Anaerobes can biodegrade benzene by using electron acceptors other than O , and this may reduce costs and exposure risks; the drawback is a remarkably slower growth rate. We evaluated a two-step strategy that involved O -dependent benzene activation and cleavage followed by intermediate oxidation coupled to NO respiration. Read More

    Establishment and characterization of a primary murine adipose tissue-chip.
    Biotechnol Bioeng 2018 Apr 24. Epub 2018 Apr 24.
    Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois.
    Better experimental models are needed to enhance our understanding of metabolic regulation which is seen in obesity and metabolic disorders, such as type 2 diabetes. In vitro models based on microfluidics enable physiological representations of tissues with several advantages over conventional culture systems, such as perfused flow to better mimic the physiological environment. Although cell lines such as 3T3-L1 have been incorporated in microfluidic devices, murine primary preadipocytes have not been differentiated and maintained for long-term monitoring in these culture systems. Read More

    Cover Image, Volume 115, Number 6, June 2018.
    Biotechnol Bioeng 2018 Jun;115(6)
    Department of Mechanical Engineering, Faculty of Science and Technology, Keio University, Kohoku-ku, Yokohama, Japan.
    The cover image, by Yuki Matsushiro et al., is based on the Article Differentiation of 3D-shape-controlled mouse neural stem cell to neural tissues in closed agarose microchambers, DOI 10.1002/bit. Read More

    An impurity characterization based approach for the rapid development of integrated downstream purification processes.
    Biotechnol Bioeng 2018 Apr 21. Epub 2018 Apr 21.
    Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York.
    In this study, we describe a new approach for the characterization of process-related impurities along with an in silico tool to generate orthogonal, integrated downstream purification processes for biological products. A one-time characterization of process-related impurities from product expression in Pichia pastoris was first carried out using linear salt and pH gradients on a library of multimodal, salt-tolerant, and hydrophobic charge induction chromatographic resins. The Reversed-phase ultra-performance liquid chromatography (UPLC) analysis of the fractions from these gradients was then used to generate large data sets of impurity profiles. Read More

    Chemically controlled aggregation of pluripotent stem cells.
    Biotechnol Bioeng 2018 Apr 21. Epub 2018 Apr 21.
    Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
    Heterogeneity in pluripotent stem cell (PSC) aggregation leads to variability in mass transfer and signaling gradients between aggregates, which results in heterogeneous differentiation and therefore variability in product quality and yield. We have characterized a chemical-based method to control aggregate size within a specific, tunable range with low heterogeneity, thereby reducing process variability in PSC expansion. This method enables controlled, scalable, stirred suspension-based manufacturing of PSC cultures that are critical for the translation of regenerative medicine strategies to clinical products. Read More

    High-efficiency affinity precipitation of multiple industrial mAbs and Fc-fusion proteins from cell culture harvests using Z-ELP-E2 nanocages.
    Biotechnol Bioeng 2018 Apr 21. Epub 2018 Apr 21.
    Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, Delaware.
    Affinity precipitation using Z-elastin-like polypeptide-functionalized E2 protein nanocages has been shown to be a promising alternative to Protein A chromatography for monoclonal antibody (mAb) purification. We have previously described a high-yielding, affinity precipitation process capable of rapidly capturing mAbs from cell culture through spontaneous, multivalent crosslinking into large aggregates. To challenge the capabilities of this technology, nanocage affinity precipitation was investigated using four industrial mAbs (mAbs A-D) and one Fc fusion protein (Fc A) with diverse molecular properties. Read More

    Stable miRNA overexpression in human CAP cells: Engineering alternative production systems for advanced manufacturing of biologics using miR-136 and miR-3074.
    Biotechnol Bioeng 2018 Apr 17. Epub 2018 Apr 17.
    Institute of Applied Biotechnology, University of Applied Sciences Biberach, Biberach, Germany.
    Chinese hamster ovary (CHO) cells still represent the major production host for therapeutic proteins. However, multiple limitations have been acknowledged leading to the search for alternative expression systems. CEVEC's amniocyte production (CAP) cells are human production cells demonstrated to enable efficient overexpression of recombinant proteins with human glycosylation pattern. Read More

    Anhydrous polymer-based coating with sustainable controlled release functionality for facile, efficacious impregnation, and delivery of antimicrobial peptides.
    Biotechnol Bioeng 2018 Apr 17. Epub 2018 Apr 17.
    Singapore Institute of Technology, Singapore, Singapore.
    Anhydrous polymers are actively explored as alternative materials to overcome limitations of conventional hydrogel-based antibacterial coating. However, the requirement for strong organic solvent in polymerization reactions often necessitates extra protection steps for encapsulation of target biomolecules, lowering encapsulation efficiency, and increasing process complexity. This study reports a novel coating strategy that allows direct solvation and encapsulation of antimicrobial peptides (HHC36) into anhydrous polycaprolactone (PCL) polymer-based dual layer coating. Read More

    Three-dimensional collagenous niche and azacytidine selectively promote time-dependent cardiomyogenesis from human bone marrow-derived MSC spheroids.
    Biotechnol Bioeng 2018 Apr 17. Epub 2018 Apr 17.
    Department of Chemical and Biomedical Engineering, Cleveland State University, Cleveland, Ohio.
    Endogenous adult cardiac regenerative machinery is not capable of replacing the lost cells following myocardial infarction, often leading to permanent alterations in structure-function-mechanical properties. Regenerative therapies based on delivering autologous stem cells within an appropriate 3D milieu could meet such demand, by enabling homing and directed differentiation of the transplanted cells into lost specialized cell populations. Since type I collagen is the predominant cardiac tissue matrix protein, we here optimized the 3D niche which could promote time-dependent evolution of cardiomyogenesis from human bone marrow-derived mesenchymal stem cells (BM-MSC). Read More

    Enhanced isobutanol production from acetate by combinatorial overexpression of acetyl-CoA synthetase and anaplerotic enzymes in engineered Escherichia coli.
    Biotechnol Bioeng 2018 Apr 17. Epub 2018 Apr 17.
    Department of Biological Engineering, College of Engineering, Konkuk University, Seoul, Korea.
    Acetic acid is an abundant material that can be used as a carbon source by microorganisms. Despite its abundance, its toxicity and low energy content make it hard to utilize as a sole carbon source for biochemical production. To increase acetate utilization and isobutanol production with engineered Escherichia coli, the feasibility of utilizing acetate and metabolic engineering was investigated. Read More

    Contributions of depth filter components to protein adsorption in bioprocessing.
    Biotechnol Bioeng 2018 Apr 16. Epub 2018 Apr 16.
    Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, Delaware.
    Depth filtration is widely used in downstream bioprocessing to remove particulate contaminants via depth straining and is therefore applied to harvest clarification and other processing steps. However, depth filtration also removes proteins via adsorption, which can contribute variously to impurity clearance and to reduction in product yield. The adsorption may occur on the different components of the depth filter, that is, filter aid, binder, and cellulose filter. Read More

    Single pass diafiltration integrated into a fully continuous mAb purification process.
    Biotechnol Bioeng 2018 Apr 16. Epub 2018 Apr 16.
    Department of Bioprocess Engineering, MedImmune, Gaithersburg, Maryland.
    The concept of continuous manufacturing has gained significant interest from the biopharmaceutical industry over the past several years. Benefits include increased manufacturing productivity, improved quality control, reduction in plant footprint, and more flexible management of facility capacity. There are several technologies currently available that enable continuous processing for chromatography and ultrafiltration. Read More

    Quantitatively characterizing drug-induced arrhythmic contractile motions of human stem cell-derived cardiomyocytes.
    Biotechnol Bioeng 2018 Apr 16. Epub 2018 Apr 16.
    Laboratoire LE2I UMR CNRS 6306, Université de Bourgogne Franche-Comté, Dijon, France.
    Quantification of abnormal contractile motions of cardiac tissue has been a noteworthy challenge and significant limitation in assessing and classifying the drug-induced arrhythmias (i.e., Torsades de pointes). Read More

    Pro region engineering of nerve growth factor by deep mutational scanning enables a yeast platform for conformational epitope mapping of anti-NGF monoclonal antibodies.
    Biotechnol Bioeng 2018 Apr 16. Epub 2018 Apr 16.
    Department of Chemical Engineering and Materials Science, Michigan State University Engineering Building, East Lansing, Michigan.
    Nerve growth factor (NGF) plays a central role in multiple chronic pain conditions. As such, anti-NGF monoclonal antibodies (mAbs) that function by antagonizing NGF downstream signaling are leading drug candidates for non-opioid pain relief. To evaluate anti-canine NGF (cNGF) mAbs we sought a yeast surface display platform of cNGF. Read More

    Single Pass Diafiltration Integrated into a Fully Continuous mAb Purification Process.
    Biotechnol Bioeng 2018 Apr 12. Epub 2018 Apr 12.
    MedImmune, Gaithersburg, MD 20878.
    The concept of continuous manufacturing has gained significant interest from the biopharmaceutical industry over the past several years. Benefits include increased manufacturing productivity, improved quality control, reduction in plant footprint, and more flexible management of facility capacity. There are several technologies currently available that enable continuous processing for chromatography and ultrafiltration. Read More

    Advances in industrial biopharmaceutical batch process monitoring: Machine-learning methods for small data problems.
    Biotechnol Bioeng 2018 Apr 6. Epub 2018 Apr 6.
    Digital Integration and Predictive Technologies, Amgen, Inc., Thousand Oaks, California.
    Biopharmaceutical manufacturing comprises of multiple distinct processing steps that require effective and efficient monitoring of many variables simultaneously in real-time. The state-of-the-art real-time multivariate statistical batch process monitoring (BPM) platforms have been in use in recent years to ensure comprehensive monitoring is in place as a complementary tool for continued process verification to detect weak signals. This article addresses a longstanding, industry-wide problem in BPM, referred to as the "Low-N" problem, wherein a product has a limited production history. Read More

    Unexpected instabilities explain batch-to-batch variability in cell-free protein expression systems.
    Biotechnol Bioeng 2018 Mar 31. Epub 2018 Mar 31.
    EMBL Australia Node for Single Molecule Science, School of Medical Sciences, University of New South Wales, Sydney, Australia.
    Cell-free methods of protein synthesis offer rapid access to expressed proteins. Though the amounts produced are generally only at a small scale, these are sufficient to perform protein-protein interaction assays and tests of enzymatic activity. As such they are valuable tools for the biochemistry and bioengineering community. Read More

    Mechanisms driving the lactate switch in Chinese hamster ovary cells.
    Biotechnol Bioeng 2018 Mar 31. Epub 2018 Mar 31.
    University of Oxford, Oxford, Oxfordshire, UK.
    The metabolism of Chinese Hamster Ovary (CHO) cells in a production environment has been extensively investigated. However, a key metabolic transition, the switch from lactate production to lactate consumption, remains enigmatic. Though commonly observed in CHO cultures, the mechanism(s) by which this metabolic shift is triggered is unknown. Read More

    Optimization of bioprocess productivity based on metabolic-genetic network models with bilevel dynamic programming.
    Biotechnol Bioeng 2018 Jul 10;115(7):1829-1841. Epub 2018 Apr 10.
    KU Leuven, Department of Chemical Engineering, Leuven, Belgium.
    One of the main goals of metabolic engineering is to obtain high levels of a microbial product through genetic modifications. To improve the productivity of such a process, the dynamic implementation of metabolic engineering strategies has been proven to be more beneficial compared to static genetic manipulations in which the gene expression is not controlled over time, by resolving the trade-off between growth and production. In this work, a bilevel optimization framework based on constraint-based models is applied to identify an optimal strategy for dynamic genetic and process level manipulations to increase productivity. Read More

    Analysis of metabolic networks of Streptomyces leeuwenhoekii C34 by means of a genome scale model: Prediction of modifications that enhance the production of specialized metabolites.
    Biotechnol Bioeng 2018 Jul 16;115(7):1815-1828. Epub 2018 Apr 16.
    Department of Chemical Engineering and Biotechnology, Centre for Biotechnology and Bioengineering (CeBiB), Universidad de Chile, Santiago, Chile.
    The first genome scale model (GSM) for Streptomyces leeuwenhoekii C34 was developed to study the biosynthesis pathways of specialized metabolites and to find metabolic engineering targets for enhancing their production. The model, iVR1007, consists of 1,722 reactions, 1,463 metabolites, and 1,007 genes, it includes the biosynthesis pathways of chaxamycins, chaxalactins, desferrioxamines, ectoine, and other specialized metabolites. iVR1007 was validated using experimental information of growth on 166 different sources of carbon, nitrogen and phosphorous, showing an 83. Read More

    Truncation of the processive Cel5A of Thermotoga maritima results in soluble expression and several fold increase in activity.
    Biotechnol Bioeng 2018 Jul 1;115(7):1675-1684. Epub 2018 May 1.
    School of Biological Sciences, University of the Punjab, Lahore, Pakistan.
    Cel5A of Thermotoga maritima, a 37 kDa cellulase of the family GH5, was expressed in partially soluble state in E. coli. However, the truncated version tCel5A1, produced by removing ten residues from the C-terminal of Cel5A, was expressed in a completely soluble form. Read More

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