Biotechnology and Bioengineering

Cover image for Vol. 115 Issue 3

Early View (Online Version of Record published before inclusion in an issue)

Edited By: Douglas S. Clark

Impact Factor: 4.481

ISI Journal Citation Reports © Ranking: 2016: 23/160 (Biotechnology & Applied Microbiology)

Online ISSN: 1097-0290


  1. 1 - 46

    1. Multi-facet implications of PEGylated lysozyme stabilized-silver nanoclusters loaded recombinant PTEN cargo in cancer theranostics

      Neha Arora, Lalitha Gavya S and Siddhartha S. Ghosh

      Version of Record online: 21 FEB 2018 | DOI: 10.1002/bit.26553

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      In this work, nanomaterial mediated intracellular delivery of functional PTEN protein was accomplished. Luminescent silver nanoclusters bound to PTEN protein were coated with polyethylene glycol to fabricate nanocomposites. Dual implication of the nanoclusters allows both tracking and delivery of the functional protein inside cancer cells; U-87 MG and MCF7. Regulation of cellular environment effectuated in reduction of cell viability of the cells, paving the way for potential PTEN based therapy.


    1. Microfluidic platforms for the study of neuronal injury in vitro

      Anil B. Shrirao, Frank H. Kung, Anton Omelchenko, Rene S. Schloss, Nada N. Boustany, Jeffrey D. Zahn, Martin L. Yarmush and Bonnie L. Firestein

      Version of Record online: 21 FEB 2018 | DOI: 10.1002/bit.26519

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      Organotypic culture of neuronal slices on a microfluidic platform designed to recreate neuronal circuitry in vitro. Controlled diffuse injury of axons isolated/guided inside microchannels interconnecting brain regions (i.e., cortex and hippocampal) is induced using pneumatic deflection of the bottom microchannel surface. Visual microscopic inspection as well as electrical characterization of axons using integrated electrode arrays are used to study neuronal degeneration and regeneration dynamics.


    1. Split trehalase as a versatile reporter for a wide range of biological analytes

      Marija Drikic and Jeroen De Buck

      Version of Record online: 21 FEB 2018 | DOI: 10.1002/bit.26556

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      In this study, Marija Drikic and Dr. Jeroen De Buck are presenting a novel split enzyme reporter method able to convert different analytes, including bacteria and antigen-specific antibodies, to glucose detectable by common glucometer. This technology, based on an engineered trehalase from E. coli, has the potential to be developed into a point-of-care biosensor able to detect different analytes in blood and other clinical samples types.

    2. Improving the recombinant human erythropoietin glycosylation using microsome supplementation in CHO cell-free system

      Chandrasekhar Gurramkonda, Aniruddha Rao, Shayan Borhani, Manohar Pilli, Sevda Deldari, Xudong Ge, Niloufar Pezeshk, Tzu-Chiang Han, Michael Tolosa, Yordan Kostov, Leah Tolosa, David W. Wood, Krishna Vattem, Douglas D. Frey and Govind Rao

      Version of Record online: 13 FEB 2018 | DOI: 10.1002/bit.26554

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      In this work, we report the production of recombinant erythropoietin (EPO) using CHO cell-free system. Using this method, EPO was expressed and purified with a two-fold increase in yield when the cell-free reaction was supplemented with CHO microsomes. The purified protein was predicted to have ∼2,300 IU in vitro activity. Additionally, we tested the presence and absence of sugars on the cell-free EPO using a lectin-based assay system. The results obtained in this study indicate that microsomes augmented in vitro production of the glycoprotein is useful for the rapid production of single doses of a therapeutic glycoprotein drug and to rapidly screen glycoprotein constructs in the development of these types of drugs. CFPS is useful for implementing a lectin-based method for rapid screening and detection of glycan moieties, which is a critical quality attribute in the industrial production of therapeutic glycoproteins.

    3. Effective role of medium supplementation in microalgal lipid accumulation

      Azadeh Fazeli Danesh, Peter Mooij, Sirous Ebrahimi, Robbert Kleerebezem and Mark van Loosdrecht

      Version of Record online: 13 FEB 2018 | DOI: 10.1002/bit.26548

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      The interaction between starch and lipid accumulation was investigated in a green microalgae enrichment culture. Two medium designs were evaluated: First a high ortho-P concentration with vitamin supplement (Pi-vitamins supplemented medium), second normal growth medium (control). The high Pi-vitamin medium clearly induced storing lipid formation while the starch accumulation was not affected. Since the starch content was identical for both treatment, orthophosphate did not act as an AGPase enzyme inhibitor in the microalgal community. This study shows a strong stimulating effect of vitamin addition on lipid production.

    4. Correlation of simulation/finite element analysis to the separation of intrinsically magnetic spores and red blood cells using a microfluidic magnetic deposition system

      Jianxin Sun, Lee Moore, Wei Xue, James Kim, Maciej Zborowski and Jeffrey J. Chalmers

      Version of Record online: 9 FEB 2018 | DOI: 10.1002/bit.26550

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      Simulated paths of RBCs of three different magnetophoretic mobilites, mean, one with 1 standard deviation above the mean, and one with 1 standard deviation below the mean, at three different injection locations. Two flow rates were used: 0.5 and 0.1 mls/hr, 9A, 9B, respectively.


    1. Glutamine synthetase gene knockout-human embryonic kidney 293E cells for stable production of monoclonal antibodies

      Da Young Yu, Sang Yoon Lee and Gyun Min Lee

      Version of Record online: 9 FEB 2018 | DOI: 10.1002/bit.26552

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      A high glutamine synthetase (GS) activity in HEK 293E cells hampers GS-mediated gene amplification and selection by methionine sulfoximine (MSX). Yu and coworkers have generated a GS-knockout HEK293E cell line using the CRISPR/Cas9 system to target the endogenous human GS gene. The GS-knockout HEK293E cell line can be successfully used as host cells for generating stable recombinant HEK293E cells producing mAb through GS-mediated gene selection.


    1. Toward industrial production of isoprenoids in Escherichia coli: Lessons learned from CRISPR-Cas9 based optimization of a chromosomally integrated mevalonate pathway

      Jorge Alonso-Gutierrez, Daisuke Koma, Qijun Hu, Yuchen Yang, Leanne J. G. Chan, Christopher J. Petzold, Paul D. Adams, Claudia E. Vickers, Lars K. Nielsen, Jay D. Keasling and Taek S. Lee

      Version of Record online: 7 FEB 2018 | DOI: 10.1002/bit.26530

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      Some of the main issues associated with E. coli as an industrial platform for isoprenoids were addressed, including an inability to grow on sucrose, a lack of endogenous control over toxic mevalonate pathway intermediates, and the limited pathway engineering into the chromosome. A new methodology for metabolic engineering of chromosomally integrated pathways is proposed using CRISPR-Cas9 to switch biological parts of the integrated pathway and lessons were presented in optimizing heterologous pathways in the chromosome.


    1. Role of respiratory terminal oxidases in the extracellular electron transfer ability of cyanobacteria

      Narendran Sekar, Jian Wang, Yan Zhou, Yi Fang, Yajun Yan and Ramaraja P. Ramasamy

      Version of Record online: 7 FEB 2018 | DOI: 10.1002/bit.26542

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      The Synechococcus elongatus mutant that lacked functional quinol oxidase (cyd) and genetically engineered to express outer membrane cytochrome (omcs) generated more photocurrent than the wild type cyanobacterium.


    1. You have full text access to this OnlineOpen article
      Using extensional flow to reveal diverse aggregation landscapes for three IgG1 molecules

      Leon F. Willis, Amit Kumar, John Dobson, Nicholas J. Bond, David Lowe, Richard Turner, Sheena E. Radford, Nikil Kapur and David J. Brockwell

      Version of Record online: 4 FEB 2018 | DOI: 10.1002/bit.26543

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      Hydrodynamic forces are implicated in biopharmaceutical aggregation, yet the ability of different fluid fields (e.g., shear or extensional flow) to trigger aggregation has remained unclear. Here, the authors subject three monoclonal antibodies to defined fluid stresses. The resulting aggregation landscapes reveal that proteins of closely related sequence can have varied aggregation behavior, potentially informing the selection of robust biopharmaceutical candidates, buffers and process conditions which minimise aggregation.

    2. Inhibition of apoptosis using exosomes in Chinese hamster ovary cell culture

      Seora Han and Won Jong Rhee

      Version of Record online: 4 FEB 2018 | DOI: 10.1002/bit.26549

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      It is important to develop a novel method for overcoming apoptosis in CHO cell culture that has less concerns for safety or cost. The authors showed for the first time that exosomes derived from CHO cells inhibited apoptosis in CHO cell culture when supplemented to the culture medium. Thus, the authors concluded that the method developed in this research may contribute to the biopharmaceutical industry where minimizing apoptosis in CHO cell culture is beneficial.

    3. Isotype dependent on-column non-reversible aggregation of monoclonal antibodies

      Monika Farys, Daniel Gibson, Alan P. Lewis, Will Lewis and Richard Kucia-Tran

      Version of Record online: 4 FEB 2018 | DOI: 10.1002/bit.26547

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      Cation exchange (CIEX) purification of mAbs has been observed to result in two-peak elution profiles and the formation of reversible and non-reversible aggregates for certain mAbs molecules. By comparing the behaviour of mAbs of different isotypes, Farys et al., have elucidated the influence of mAb isotype, and the specific constant domains involved in causing two-peak elution profiles. Meanwhile comparison of IgG4s with different variable domains revealed the synergistic influence of the variable domain upon non-reversible protein aggregation during CIEX chromatography.

    4. From lab to market: An integrated bioprocess design approach for new-to-nature biosurfactants produced by Starmerella bombicola

      Lisa Van Renterghem, Sophie L.K.W. Roelants, Niki Baccile, Katrijn Uyttersprot, Marie Claire Taelman, Bernd Everaert, Stein Mincke, Sam Ledegen, Sam Debrouwer, Kristel Scholtens, Christian Stevens and Wim Soetaert

      Version of Record online: 4 FEB 2018 | DOI: 10.1002/bit.26539

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      In this paper, Van Renterghem et al. (2017) scale up the production of a newly discovered glycolipid microbial biosurfactant, namely bolaform SLs. After purification, the application potential was assessed and this unravels very interesting results. However, due to its lower chemical stability and therefore limiting its application potential, the production is redirected towards a more stable biosurfactant by applying an integrated bioprocess design strategy. The latter has proven to be key to bring microbial biosurfactants closer to the market.

    5. Selective production of decanoic acid from iterative reversal of β-oxidation pathway

      Seohyoung Kim and Ramon Gonzalez

      Version of Record online: 4 FEB 2018 | DOI: 10.1002/bit.26540

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      Selective synthesis of carboxylic acids of a specific carbon-chain length through iterative pathways like the ß-oxidation reversal (r-BOX) and fatty acid biosynthesis (FAB) has been hampered by the broad chain-length specificity of r-BOX and FAB enzymes. In this study, we exploited the overlapping chain-length specificity of certain r-BOX and thioesterase enzymes to selectively generate decanoic acid (DA). Upon implementation of this design in combination with chromosomal and episomal expression of r-BOX enzymes and use of a dodecane overlay, we achieved the synthesis of DA at high yield and titer.

    6. High titer oncolytic measles virus production process by integration of dielectric spectroscopy as online monitoring system

      Tanja A. Grein, Daniel Loewe, Hauke Dieken, Denise Salzig, Tobias Weidner and Peter Czermak

      Version of Record online: 4 FEB 2018 | DOI: 10.1002/bit.26538

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      Dielectric spectroscopy enables the monitoring of cell adhesion on the microcarrier, cell concentration and the identification of the optimal virus harvest time. We found that the maximum Measles virus titer was achieved approximately 40 hr after the permittivity maximum. Compared to an uncontrolled Measles virus production process, the integration of DS increased reproducible the maximum virus concentration by more than three orders of magnitude.

    7. Consolidated bioprocessing of lignocellulosic biomass to lactic acid by a synthetic fungal-bacterial consortium

      Robert L. Shahab, Jeremy S. Luterbacher, Simone Brethauer and Michael H. Studer

      Version of Record online: 1 FEB 2018 | DOI: 10.1002/bit.26541

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      In this work, the direct production of lactic acid from pretreated lignocellulosic biomass by a synthetic microbial consortium was demonstrated. The cellulolytic enzymes producing aerobic fungus Trichoderma reesei and facultative anaerobic lactic acid bacteria with the capability to utilize both hexoses and pentoses were co-cultivated in a membrane-aerated biofilm reactor. Metabolic compartmentalization and spatial structuring allowed the formation of stable artificial cooperator-cheater communities thereby showing the potential of engineering microbial consortia for consolidated bioprocessing of lignocellulosic biomass.

    8. Enrichment of high affinity subclasses and glycoforms from serum-derived IgG using FcγRs as affinity ligands

      Austin W. Boesch, James H. Kappel, Alison E. Mahan, Thach H. Chu, Andrew R. Crowley, Nana Y. Osei-Owusu, Galit Alter and Margaret E. Ackerman

      Version of Record online: 1 FEB 2018 | DOI: 10.1002/bit.26545

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      Boesch and coworkers demonstrate the use the of FcgRs as affinity ligands to enrich natural human IgG glycoforms and subclass variants. Structure-function relationships of these enriched fractions were further characterized using cell based assays such as Natural Killer cell degranulation and Monocyte mediated phagocytosis. This work demonstrates a tractable means to rapidly distinguish complex functional relationships between two or more interacting biological agents by leveraging affinity chromatography followed by secondary analysis with high-resolution biophysical and functional assays.

    9. Modeling and optimization of lipid accumulation by Yarrowia lipolytica from glucose under nitrogen depletion conditions

      Carlos E. Robles-Rodríguez, Rafael Muñoz-Tamayo, Carine Bideaux, Nathalie Gorret, Stéphane E. Guillouet, Carole Molina-Jouve, Gilles Roux and César A. Aceves-Lara

      Version of Record online: 31 JAN 2018 | DOI: 10.1002/bit.26537

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      Two mathematical models for lipid production by Yarrowia lipolytica are developed. The Droop model for microalgae is extended for yeast. The models are calibrated and validated with independent data sets. Multi objective optimization of lipid accumulation is studied with the quota model. A simple control strategy for critical quota is promising to optimize lipid productivity.

      This work presents two mathematical models of the metabolism of Yarrowia lipolytica. The first model is based on Monod and inhibition kinetics, and the second one is based on the Droop quota model approach. The quota based model was used for maximizing lipid productivity and lipid content in simulation.

    10. Methanol independent induction in Pichia pastoris by simple derepressed overexpression of single transcription factors

      Thomas Vogl, Lukas Sturmberger, Pia C. Fauland, Patrick Hyden, Jasmin E. Fischer, Christian Schmid, Gerhard G. Thallinger, Martina Geier and Anton Glieder

      Version of Record online: 29 JAN 2018 | DOI: 10.1002/bit.26529

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      In the commonly used protein production host Komagataella phaffii (Pichia pastoris), methanol-inducible promoters are used because of their tight regulation and exceptional strength. Yet, induction with toxic and flammable methanol can be a considerable safety risk and cannot be applied in many existing fermentation plants. Here, we report the conversion of existing methanol based production strains into glucose/glycerol regulated, methanol-free systems by derepressed overexpression of a single transcription factor.

    11. Gold nanorod-photosensitizer conjugates with glutathione-sensitive linkages for synergistic cancer photodynamic/photothermal therapy

      Jongseon Choi, Sang-Eun Lee, Jeong-Sook Park and So Yeon Kim

      Version of Record online: 29 JAN 2018 | DOI: 10.1002/bit.26536

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      Recently, photodynamic therapy and NIR photothermal therapy using gold nanocarriers have attracted particular interest in the treatment of various cancers. Kim and coworkers developed the tumor-targeting AuNR-photosensitizer conjugates with glutathione-sensitive linkages for synergistic cancer photodynamic/photothermal therapy. AuNR-photosensitizer conjugates showed more than 99% in vitro cellular uptake in MCF7 cells. FA-PEG-P(Asp)-DHLA-AuNR100-SS-Ce6 with a 3.84 aspect ratio exhibited strong photothermal effects, enhanced singlet oxygen generation, and marked phototoxicity compared with free PS after laser irradiation.

    12. 3D stromal tissue equivalent affects intestinal epithelium morphogenesis in vitro

      Vincenza De Gregorio, Giorgia Imparato, Francesco Urciuolo and Paolo A. Netti

      Version of Record online: 24 JAN 2018 | DOI: 10.1002/bit.26522

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      In this work, an engineered organotypic model of human intestine equivalent composed by a well-polarized epithelium and an intestinal stromal equivalent with cell-synthesized ECM has been developed to study in vitro the epithelial/ECM interactions in comparison with a 3D bovine collagen based model and a 2D transwell culture. This fully functional human intestinal organotypic model provides a new platform for the assessment of pharmaco-toxicity studies as well as for preclinical studies of mucosal immunology and bowel inflammation.

    13. Development of a temperature-responsive yeast cell factory using engineered Gal4 as a protein switch

      Pingping Zhou, Wenping Xie, Zhen Yao, Yongqiang Zhu, Lidan Ye and Hongwei Yu

      Version of Record online: 24 JAN 2018 | DOI: 10.1002/bit.26544

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      This work presents a temperature-dependent dynamic control strategy for yeast developed based on directed evolution of the transcriptional activator Gal4, which facilitates decoupling of cell growth and product accumulation in fermentation of secondary metabolites, exemplified by lycopene, and may provide a viable approach to biosynthesis of heterologous proteins or metabolites that are toxic to the host cells.

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      Botulinum hemagglutinin-mediated in situ break-up of human induced pluripotent stem cell aggregates for high-density suspension culture

      Suman C. Nath, Tomohiro Tokura, Mee-Hae Kim and Masahiro Kino-oka

      Version of Record online: 24 JAN 2018 | DOI: 10.1002/bit.26526

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      We established a simple method for aggregate break-up into small ones by revealing the temporary effect of botulinum hemagglutinin which specifically bound with E-cadherin, and disrupted cell–cell connections in hiPSCs aggregate in suspension culture. This approach obviated the need for enzymatic treatment for aggregate break-up into small ones for achieving a high cell density in suspension culture.

    15. Computer-assisted engineering of hyperstable fibroblast growth factor 2

      Pavel Dvorak, David Bednar, Pavel Vanacek, Lukas Balek, Livia Eiselleova, Veronika Stepankova, Eva Sebestova, Michaela Kunova Bosakova, Zaneta Konecna, Stanislav Mazurenko, Antonin Kunka, Tereza Vanova, Karolina Zoufalova, Radka Chaloupkova, Jan Brezovsky, Pavel Krejci, Zbynek Prokop, Petr Dvorak and Jiri Damborsky

      Version of Record online: 24 JAN 2018 | DOI: 10.1002/bit.26531

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      The applications of fibroblast growth factors FGFs for stem cells cultivation and protein therapies are often limited by low stability of these proteins. Here the authors describe engineering hyperstable FGF2 molecule with melting temperature increased by 19 °C and in vitro functional half-life at 37 °C improved from 10 hr to more than 20 days. This stabilization was achieved by a computer-assisted engineering strategy combining energy-based and evolution-based analyses with focused directed evolution and unique functional screening of novel variants.

    16. Modulation of saturation and chain length of fatty acids in Saccharomyces cerevisiae for production of cocoa butter-like lipids

      David Bergenholm, Michael Gossing, Yongjun Wei, Verena Siewers and Jens Nielsen

      Version of Record online: 24 JAN 2018 | DOI: 10.1002/bit.26518

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      Microbial production of cocoa butter requires modification of fatty acid chain length and saturation of the host organism Saccharomyces cerevisiae. Altering the activity of the fatty acid biosynthetic and modifying enzymes Ole1p, Acc1p, and Elo1p changes the fatty acid composition favorably. The modifications lead to an increased content of saturated fatty acids and an increased production of cocoa butter lipids.

    17. Precision-porous templated scaffolds of varying pore size drive dendritic cell activation

      Ruying Chen, Hongyan Ma, Lei Zhang and James D. Bryers

      Version of Record online: 22 JAN 2018 | DOI: 10.1002/bit.26532

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      Here, Chen and co- workers employ a precision templating method to make 3-D porous polymer scaffolds with uniformly defined and adjustable porous structure. Without the use of dendritic cell chemo-attractants or chemical adjuvants, results suggest that dendritic cell maturation, and scaffold infiltration profile can be modulated by simply altering the pore size of the scaffolds, independent of the polymer used. These findings will have broader implications in the area of immunotherapy and vaccine delivery.

    18. A robust protocol for directed aryl sulfotransferase evolution toward the carbohydrate building block GlcNAc

      Shohana Islam, Diana M. Mate, Ronny Martínez, Felix Jakob and Ulrich Schwaneberg

      Version of Record online: 22 JAN 2018 | DOI: 10.1002/bit.26535

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      A directed aryl sulfotransferase evolution protocol was successfully validated for enhancing the specific activity toward a monosaccharide, N-acetylglucosamine (GlcNAc). A random mutagenesis library of aryl sulfotransferase B (ASTB) from Desulfitobacteroium hafniense was generated using SeSaM method and screened via advanced and optimized pNPS-based screening system as an example for small sugar molecule, GlcNAc. The identified “best” variant (ASTB-V1) was characterized in terms of specific activity and product determination using HPLC/MS.

    19. Manipulation of the sodium-potassium ratio as a lever for controlling cell growth and improving cell specific productivity in perfusion CHO cell cultures

      Samantha B. Wang, Alexandria Lee-Goldman, Janani Ravikrishnan, Lili Zheng and Henry Lin

      Version of Record online: 22 JAN 2018 | DOI: 10.1002/bit.26527

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      Contour plots of different sodium and potassium ratios in perfusion medium reveal higher levels of potassium decrease cell growth and significantly increase CHO cell production of recombinant protein.

    20. Identification of process conditions influencing protein aggregation in Chinese hamster ovary cell culture

      Albert J. Paul, René Handrick, Sybille Ebert and Friedemann Hesse

      Version of Record online: 22 JAN 2018 | DOI: 10.1002/bit.26534

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      New analytical methods for the characterization of mAb aggregation enabled rapid and efficient bioprocess optimization of mammalian cells. Using design of experiments (DoE) strategies, important bioprocess variables influencing the aggregation of mAb and host cell proteins were identified and further investigated in order to find optimal conditions for the reduction of protein aggregation during cell culture. Finally, the aggregation reducing conditions were verified and applied to another production system using a different bioprocess medium and another CHO cell line producing another mAb.

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      Protein-engineering of chitosanase from Bacillus sp. MN to alter its substrate specificity

      Eva K. Regel, Tobias Weikert, Anna Niehues, Bruno M. Moerschbacher and Ratna Singh

      Version of Record online: 19 JAN 2018 | DOI: 10.1002/bit.26533

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      Protein-engineering of Bacillus sp. MN chitosanase alters its substrate specificity on partially acetylated chitosan polymers. In contrast to the wild-type enzyme, two muteins with active site substitutions accept N-acetyl-D-glucosamine units at their subsite (−2) when hydrolyzing chitosans. As the substrate specificity of the enzyme determines the composition of the oligomeric products, this approach overcomes limitations associated with naturally occurring enzymes and expands the spectrum of defined producible chitooligosaccharides.

    22. Perfusion applied to a 3D model of bone metastasis results in uniformly dispersed mechanical stimuli

      Boyuan Liu, Suyue Han, Brandon P. Hedrick, Yahya Modarres-Sadeghi and Maureen E. Lynch

      Version of Record online: 19 JAN 2018 | DOI: 10.1002/bit.26524

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      Breast cancer cells preferentially metastasize to the skeleton and experience mechanical signals such as fluid flow. We created a full-scale computational model of applied perfusion in a 3D model of bone metastasis to predict the mechanical environment during experimentation. Applied fluid flow resulted in heterogeneous fluid velocities and wall shear stresses that were evenly distributed through the scaffold, and their distributions persisted with varying sub-domain diameter and location. These results indicate that local populations of cells throughout the scaffold experience similar mechanical microenvironments.

    23. Central pathway engineering for enhanced succinate biosynthesis from acetate in Escherichia coli

      Bing Huang, Hao Yang, Guochen Fang, Xing Zhang, Hui Wu, Zhimin Li and Qin Ye

      Version of Record online: 19 JAN 2018 | DOI: 10.1002/bit.26528

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      In this study, acetate was used as carbon source to produce succinate by engineered E. coli. A serial of metabolic engineering strategies, including reducing OAA decarboxylation, engineering TCA cycle, enhancement of acetate assimilation pathway, and increasing aerobic ATP supply through cofactor engineering, were applied to increase acetate assimilation and succinate production. The result suggested that the metabolically engineered E. coli strains would have great potential to produce succinate from acetate, and acetate can be an alternative carbon source to produce high value-added chemicals.

    24. Engineering and cytosolic delivery of a native regulatory protein and its variants for modulation of ERK2 signaling pathway

      Jeong-Hyun Ryou, Yoo-Kyoung Sohn, Dong-Gun Kim, Hyun-Ho Kyeong and Hak-Sung Kim

      Version of Record online: 16 JAN 2018 | DOI: 10.1002/bit.26516

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      A stronger ERK2 blocker, PEA-16, was developed based on semi-rational approach, leading to about an 830-fold increase in the binding affinity. Furthermore, a cytosolic delivery of PEA-16 using bacterial toxin-based delivery system resulted in an effective suppression of cell proliferation through the inhibition of the ERK2-mediated cell signaling. This strategy can be widely used in modulating the cell signaling pathways for the development of therapeutics as well as biological study.

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      Thermoactivation of a cellobiohydrolase

      Peter Westh, Kim Borch, Trine Sørensen, Radina Tokin, Jeppe Kari, Silke Badino, Mafalda A. Cavaleiro, Nanna Røjel, Stefan Christensen, Cynthia S. Vesterager and Corinna Schiano-di-Cola

      Version of Record online: 16 JAN 2018 | DOI: 10.1002/bit.26513

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      Cellulases acting on their insoluble substrate are often only moderately accelerated by temperature even in the range, where the enzymes are stable. We suggest that this reflects a pronounced temperature induced dissociation from the substrate, and show that enzyme engineering can reduce this dissociation and hence promote thermoactivation of a cellulose. This avenue towards better activity at high temperature could become useful in industrial design of cellulases.

    26. Engineered cell migration to lesions linked to autoimmune disease

      Abdullah Al Mosabbir, Anam Qudrat and Kevin Truong

      Version of Record online: 8 JAN 2018 | DOI: 10.1002/bit.26523

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      Autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and Crohn's disease often manifests as the formation of lesions that feature a high local concentration of granulocyte-macrophage colony-stimulating factor (GM-CSF). Using a protein engineering approach, we have engineered cellular chemotaxis towards the GM-CSF cytokine as a tool to deliver therapeutic cells to the site of autoimmune lesions.

    27. Fabrication and evaluation of 3D printed BCP scaffolds reinforced with ZrO2 for bone tissue applications

      Min-Woo Sa, Bao-Ngoc B. Nguyen, Rebecca A. Moriarty, Timur Kamalitdinov, John P. Fisher and Jong Young Kim

      Version of Record online: 8 JAN 2018 | DOI: 10.1002/bit.26514

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      Differentiation studies of human mesenchymal stem cells (hMSCs) on 3D-printed BCP/ZrO2 scaffolds in static and dynamic culture conditions showed increased expression of bone morphogenic protein-2 (BMP-2) when cultured on BCP/ZrO2 scaffolds under dynamic conditions compared to on BCP control scaffolds.

    28. Engineering tunable biosensors for monitoring putrescine in Escherichia coli

      Xue-Feng Chen, Xiao-Xia Xia, Sang Yup Lee and Zhi-Gang Qian

      Version of Record online: 8 JAN 2018 | DOI: 10.1002/bit.26521

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      The authors present the design, construction, and fine-tuning of transcriptional factor PuuR-based biosensors for monitoring putrescine, an important member of biological polyamines, in Escherichia coli. The engineered biosensors were specific for putrescine, and their performance could be modulated at the genetic level by manipulation of the expression level of PuuR, its cognate promoter, the chromosomal genes involved in putrescine biosynthesis, and at the cell population level by altering growth medium of the biosensor strains.

    29. Metabolic characterization of anaerobic fungi provides a path forward for bioprocessing of crude lignocellulose

      John K. Henske, St. Elmo Wilken, Kevin V. Solomon, Chuck R. Smallwood, Vaithiyalingam Shutthanandan, James E. Evans, Michael K. Theodorou and Michelle A. O'Malley

      Version of Record online: 8 JAN 2018 | DOI: 10.1002/bit.26515

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      Anaerobic gut fungi regulate the expression of their enzymes, which can be used to harness their cellulolytic capabilities for bioprocessing. A two-stage process was developed to utilize the diverse, excess sugars unlocked by the fungal enzymes acting on unpretreated lignocellulose during growth.

    30. Modeling electron competition among nitrogen oxides reduction and N2O accumulation in hydrogenotrophic denitrification

      Yiwen Liu, Huu H. Ngo, Wenshan Guo, Lai Peng, Xueming Chen, Dongbo Wang, Yuting Pan and Bing-Jie Ni

      Version of Record online: 8 JAN 2018 | DOI: 10.1002/bit.26512

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      The model describes electron competition during hydrogenotrophic denitrification. The model was validated by two independent hydrogenotrophic denitrifying cultures. Model indicates insignificant N2O accumulation under hydrogen limiting conditions.

    31. Hypoxia and transforming growth factor-beta1 pathway activation promote Chinese Hamster Ovary cell aggregation

      Yueming Qian, Matthew S. Rehmann, Nan-Xin Qian, Aiqing He, Michael C. Borys, Paul S. Kayne and Zheng Jian Li

      Version of Record online: 8 JAN 2018 | DOI: 10.1002/bit.26520

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      Hypoxia has been identified to be a cause for promoting CHO cell aggregation. Hypoxic conditions increase TGF-beta production and activate its pathway, leading to increased production of extracellular matrix proteins. Extracellular matrix proteins in turn form networks gathering the cells.


    1. Advances in applications of rhamnolipids biosurfactant in environmental remediation: A review

      Guansheng Liu, Hua Zhong, Xin Yang, Yang Liu, Binbin Shao and Zhifeng Liu

      Version of Record online: 3 JAN 2018 | DOI: 10.1002/bit.26517

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      Production, molecular structures, physiochemical, and biological properties of rhamnolipids, and application of rhamnolipid in bioremediation, soil washing, and phytoremediation for removal of hydrophobic organic contaminants (HOCs) and heavy metals, are reviewed.


    1. Vitamin B12 association with mAbs: Mechanism and potential mitigation strategies

      Cheng Du, Robert Martin, Yunping Huang, Ameya Borwankar, Zhijun Tan, Jay West, Nripen Singh, Michael Borys, Sanchayita Ghose, Richard Ludwig, Li Tao and Zheng Jian Li

      Version of Record online: 19 DEC 2017 | DOI: 10.1002/bit.26511

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      A novel post-translational modification of monoclonal antibodies (mAbs) by vitamin B12 is reported. This modification is a second-order reaction depending on concentrations of both free sulfhydryl groups on reduced mAb and hydroxocobalamin, the active form of vitamin B12. Light can convert inactive form of vitamin B12 in culture media into active form and the activating wavelengths are identified. In process control strategies are discussed ensure product quality, safety and lot to lot consistency for manufacturing biologics.

    2. You have full text access to this OnlineOpen article
      Paramagnetism in Bacillus spores: Opportunities for novel biotechnological applications

      Ke Xu Zhou, Adrian Ionescu, Eamon Wan, Yeuk N. Ho, Crispin H.W. Barnes, Graham Christie and D. Ian Wilson

      Version of Record online: 15 DEC 2017 | DOI: 10.1002/bit.26501

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      Spores of Bacillus megaterium, Bacillus cereus, and Bacillus subtilis were found to exhibit intrinsic paramagnetic properties as a result of the accumulation of manganese ions both within the spore as well as on its surface. All three Bacillus species displayed strong yet distinctive magnetic properties arising from differences in manganese quantity and valency. Three spore-related biotechnological applications—magnetic sensing, magnetic separation and metal ion adsorption—were assessed, with the latter two considered as having the most potential for development.

    3. Growth modeling of the green microalga Scenedesmus obliquus in a hybrid photobioreactor as a practical tool to understand both physical and biochemical phenomena in play during algae cultivation

      Deise P. Tramontin, Pablo D. Gressler, Leonardo R. Rörig, Roberto B. Derner, Jurandir Pereira-Filho, Claudemir M. Radetski and Marintho B. Quadri

      Version of Record online: 15 DEC 2017 | DOI: 10.1002/bit.26510

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      A novel type of hybrid photobioreactor, combining the characteristics of thin layer cascade systems with the tubular photobioreactors showed high productivity and improved use of CO2 injected under varying light and temperature conditions. The authors developed a mathematical model of algal growth in the system, which described the process satisfactorily and allowed to optimize operational variables. The model presents relatively simple input parameters and is based on knowledge about the geometry of the system, the local environmental conditions and the microorganism to be used.


    1. Production of cellulosic organic acids via synthetic fungal consortia

      Scott A. Scholz, Ian Graves, Jeremy J. Minty and Xiaoxia N. Lin

      Version of Record online: 15 DEC 2017 | DOI: 10.1002/bit.26509

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      Scholz and coworkers developed a consolidated bioprocessing system that supports all of the steps required for conversion of lignocellulosic biomass to two organic acids, including cell growth, cellulase enzyme production, lignocellulose hydrolysis, and organic acid production. This process was achieved in a minimal medium, without supplementation of expensive nutrients, by pairing the cellulolytic specialist Trichoderma reesei and a furmaric acid or lactic acid producing fungal specialist into a functional synthetic consortium.


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      cGMP production and analysis of BG505 SOSIP.664, an extensively glycosylated, trimeric HIV-1 envelope glycoprotein vaccine candidate

      Antu K. Dey, Albert Cupo, Gabriel Ozorowski, Vaneet K. Sharma, Anna-Janina Behrens, Eden P. Go, Thomas J. Ketas, Anila Yasmeen, Per J. Klasse, Eddy Sayeed, Heather Desaire, Max Crispin, Ian A. Wilson, Rogier W. Sanders, Thomas Hassell, Andrew B. Ward and John P. Moore

      Version of Record online: 11 DEC 2017 | DOI: 10.1002/bit.26498

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      The paper describes the production and properties of the BG505 SOSIP.664 HIV-1 envelope glycoprotein trimer under cGMP conditions. This complex, highly glycosylated and conformationally sensitive protein complex is the first of a new generation of immunogens designed to mimic the structure of the envelope spikes present on the surface of HIV-1 virus particles.


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