Biotechnology and Bioengineering

Cover image for Vol. 110 Issue 5

May 2013

Volume 110, Issue 5

Pages C1–C1, fmi–fmvi, 1255–1527

  1. Cover

    1. Top of page
    2. Cover
    3. Contents
    4. Spotlights
    5. Review
    6. Articles
    7. Communication to the Editor
    8. Errata
    1. You have free access to this content
      Biotechnology and Bioengineering: Volume 110, Number 5, May 2013 (page C1)

      Version of Record online: 20 MAR 2013 | DOI: 10.1002/bit.24662

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      Cover Legend Vero cells growing adherent to microcarriers. (Image courtesy of Dr. Yvonne E. Thomassen et. al.)

  2. Contents

    1. Top of page
    2. Cover
    3. Contents
    4. Spotlights
    5. Review
    6. Articles
    7. Communication to the Editor
    8. Errata
  3. Spotlights

    1. Top of page
    2. Cover
    3. Contents
    4. Spotlights
    5. Review
    6. Articles
    7. Communication to the Editor
    8. Errata
  4. Review

    1. Top of page
    2. Cover
    3. Contents
    4. Spotlights
    5. Review
    6. Articles
    7. Communication to the Editor
    8. Errata
    1. Review

      An 'omics approach towards CHO cell engineering (pages 1255–1271)

      Payel Datta, Robert J. Linhardt and Susan T. Sharfstein

      Version of Record online: 4 FEB 2013 | DOI: 10.1002/bit.24841

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      Chinese hamster ovary(CHO) cells have been extensively utilized for industrial production of biopharmaceuticals. The sequencing of the CHO genome has provided new avenues for CHO cell engineering to improve productivity, increase robustness, and permit production of novel bioproducts. This review details advances in the use of 'omics technologies to gain fundamental understanding of CHO cell physiology and improve CHO-cell engineering.

  5. Articles

    1. Top of page
    2. Cover
    3. Contents
    4. Spotlights
    5. Review
    6. Articles
    7. Communication to the Editor
    8. Errata
    1. Editors' Choice

      Functional motor recovery is improved due to local placement of GDNF microspheres after delayed nerve repair (pages 1272–1281)

      Matthew D. Wood, Tessa Gordon, Stephen W.P. Kemp, Edward H. Liu, Howard Kim, Molly S. Shoichet and Gregory H. Borschel

      Version of Record online: 4 JAN 2013 | DOI: 10.1002/bit.24800

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      Bioengineering strategies to promote peripheral nerve regeneration after injury tend to focus on therapies to bridge large nerve defects with fewer therapies developed to treat other nerve injuries, such as delayed repair following nerve transection. The authors constructed delivery systems using fibrin gels containing either free GDNF or polylactide–glycolic acid (PLGA) microspheres with GDNF to treat delayed nerve repair. GDNF microspheres improved axonal regeneration and functional motor outcomes, such as improved contractile muscle force and preservation of muscle mass.

    2. Biocatalysis, Protein Engineering, and Nanobiotechnology

      Whole-cell-based CYP153A6-catalyzed (S)-limonene hydroxylation efficiency depends on host background and profits from monoterpene uptake via AlkL (pages 1282–1292)

      Sjef Cornelissen, Mattijs K. Julsing, Jan Volmer, Ole Riechert, Andreas Schmid and Bruno Bühler

      Version of Record online: 9 FEB 2013 | DOI: 10.1002/bit.24801

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      For cytochrome P450-based hydroxylation of (S)-limonene to (S)-perillyl alcohol by recombinant Pseudomonas putida, side product formation due to host intrinsic dehydrogenases and substrate mass transfer were found to be the most critical factors determining the efficiency of the two-liquid phase biotransformation. Undesired perillyl alcohol oxidation was successfully reduced by choosing E. coli as recombinant host. Limonene hydroxylation rates were improved by introducing the outer membrane protein AlkL, which represents a promising general strategy to enhance hydrophobic substrate uptake.

    3. Comparative characterization of novel ene-reductases from cyanobacteria (pages 1293–1301)

      Yilei Fu, Kathrin Castiglione and Dirk Weuster-Botz

      Version of Record online: 21 JAN 2013 | DOI: 10.1002/bit.24817

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      Ene-reductases are capable of reducing alkenes in a trans-specific fashion, which is one of the most employed reactions for the production of chiral molecules. In this study, nine ene-reductases from different cyanobacterial strains were characterized. Enzymes were identified with high activities towards a broad spectrum of alkenes. In addition to NADPH as cofactor, NADH was accepted with moderate to high rates as well. Excellent stereoselectivities were achieved of up to 99 % de and 99 % ee.

    4. Biofuels and Environmental Biotechnology

      Continuous SSCF of AFEX™ pretreated corn stover for enhanced ethanol productivity using commercial enzymes and Saccharomyces cerevisiae 424A (LNH-ST) (pages 1302–1311)

      Mingjie Jin, Christa Gunawan, Venkatesh Balan, Xiurong Yu and Bruce E. Dale

      Version of Record online: 29 DEC 2012 | DOI: 10.1002/bit.24797

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      Productivity is a critical factor limiting commercialization of cellulosic ethanol. This work studied the kinetics of batch SHF (separate hydrolysis and fermentation) process and batch SSCF (simultaneous saccharification and co-fermentation) process on AFEX™ pretreated corn stover and designed a continuous SSCF process for enhancement of ethanol productivity.

    5. Modeling and optimization of granulation process of activated sludge in sequencing batch reactors (pages 1312–1322)

      Kui-Zu Su, Bing-Jie Ni and Han-Qing Yu

      Version of Record online: 17 JAN 2013 | DOI: 10.1002/bit.24812

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      By taking into account all of the key steps including biomass growth, increase in particle size and density, detachment, breakage and sedimentation, a mathematical model was developed to simulate the granulation process of activated sludge. Mean radius, biomass discharge ratio, total number and bioparticle size distribution were predicted well with the model. Optimum characteristics of aerobic granules were predicted aiming at both high settling velocity and substrate utilization rate, and the corresponding optimum operating conditions were determined.

    6. Biofilm model calibration and microbial diversity study using Monte Carlo simulations (pages 1323–1332)

      D. Brockmann, A. Caylet, R. Escudié, J.-P. Steyer and N. Bernet

      Version of Record online: 17 JAN 2013 | DOI: 10.1002/bit.24818

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      Microbial diversity in attached and suspended biomass of a biofilm reactor was studied using a highly discretized multi-species biofilm model. Monte Carlo simulations showed that both attached and suspended biomass is dominated by the same bacterial group. In addition, detachment of biomass from the biofilm surface highly influences microbial competition in the bulk liquid.

    7. Global gene expression of Dehalococcoides within a robust dynamic TCE-dechlorinating community under conditions of periodic substrate supply (pages 1333–1341)

      Kimberlee A. West, Patrick K.H. Lee, David R. Johnson, Stephen H. Zinder and Lisa Alvarez-Cohen

      Version of Record online: 9 FEB 2013 | DOI: 10.1002/bit.24819

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      A genus-wide microarray targeting Dehalococcoides (Dhc) was used to examine the transcriptional dynamics within an undefined microbial community, the robust trichloroethene-degrading ANAS consortia, at three time-points within a reductive dechlorination feast and famine feeding cycle. The temporal cycle resembles environmental communities which undergo nutrient flux such as biostimulation. Results indicate efficient transcription and regulation of the streamlined Dhc genome, with special attention given to reductive dehalogenase genes, hydrogenase genes, and genes involved in cobalamin biosynthesis and transport.

    8. Bioprocess Engineering and Supporting Technologies

      Identification and quantitation of vesivirus 2117 particles in bioreactor fluids from infected Chinese hamster ovary cell cultures (pages 1342–1353)

      Yongchang Qiu, Nathan Jones, Michelle Busch, Peng Pan, Jesse Keegan, Weichang Zhou, Mark Plavsic, Michael Hayes, John M. McPherson, Tim Edmunds, Kate Zhang and Robert J. Mattaliano

      Version of Record online: 25 DEC 2012 | DOI: 10.1002/bit.24791

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      Qiu and coworkers describe the successful application of mass spectrometry-based protein profiling in identification and quantitation of contaminating virus from complex bioreactor fluids.

    9. Scale-down of the inactivated polio vaccine production process (pages 1354–1365)

      Yvonne E. Thomassen, Aart G. van 't Oever, Marian Vinke, Arjen Spiekstra, René H. Wijffels, Leo A. van der Pol and Wilfried A.M. Bakker

      Version of Record online: 29 DEC 2012 | DOI: 10.1002/bit.24798

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      An up-to-date lab-scale version encompassing the legacy inactivated polio vaccine production process was set-up. The production process, consisting of Vero cell culture, poliovirus culture, the subsequent purification using filtration and chromatography units and inactivation procedure was scaled-down. The followed approach was initial scale-down of the separate unit operations at setpoint and subsequent, application of the unit operations successively in a comparative manner to large-scale manufacturing. With this scale-down model representative trivalent vaccine can be made.

    10. Permeability of a growing biofilm in a porous media fluid flow analyzed by magnetic resonance displacement-relaxation correlations (pages 1366–1375)

      Sarah J. Vogt, Alexis B. Sanderlin, Joseph D. Seymour and Sarah L. Codd

      Version of Record online: 29 DEC 2012 | DOI: 10.1002/bit.24803

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      The experimental observation of biofilm growth in porous media is complicated by the heterogeneous nature of the biofilm and of the porous media growth environments and the amount of convective flow through the biofilm in a biofouled porous media is currently an open question. A recently developed magnetic resonance (MR) experimental technique, displacement-relaxation correlation, allows the displacements of fluid in the biofilm to be distinguished from those in the open pores by separating the MR signal based on the T2 relaxation and attempts to address this question.

    11. Development of a new bioprocess scheme using frozen seed train intermediates to initiate CHO cell culture manufacturing campaigns (pages 1376–1385)

      Gargi Seth, Robert W. Hamilton, Thomas R. Stapp, Lisa Zheng, Angela Meier, Krista Petty, Stephenie Leung and Srikanth Chary

      Version of Record online: 4 JAN 2013 | DOI: 10.1002/bit.24808

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      FASTEC (Frozen Accelerated Seed Train for Execution of a Campaign) approach involves initiating cell culture manufacturing campaigns with CHO cells cryopreserved in large volume bags (FROSTIs- Frozen Seed Train Intermediates). Each FROSTI thaw to initiate an inoculum train for a manufacturing campaign provides the same starting point and cell source for each run.

    12. Non-invasive online detection of microbial lysine formation in stirred tank bioreactors by using calorespirometry (pages 1386–1395)

      Lars Regestein, Thomas Maskow, Andreas Tack, Ingo Knabben, Martin Wunderlich, Johannes Lerchner and Jochen Büchs

      Version of Record online: 17 JAN 2013 | DOI: 10.1002/bit.24815

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      Non-invasive methods for online monitoring of biotechnological processes without compromising the integrity of the reactor system are very important to generate continuous data. Thus, this article demonstrates a calorespirometric method for online detection of microbial lysine formation in stirred tank bioreactors. The respective heat generation of two bacterial strains, Corynebacterium glutamicum ATCC 13032 (wild-type) and C. glutamicum DM1730 (lysine producer) was compared with the O2-consumption in order to determine whether lysine was formed.

    13. Cellular and Metabolic Engineering

      Real-time detection of cellular death receptor-4 activation by fluorescence resonance energy transfer (pages 1396–1404)

      Zeynep Dereli-Korkut, Harmeet Gandhok, Ling Ge Zeng, Sidra Waqas, Xuejun Jiang and Sihong Wang

      Version of Record online: 17 JAN 2013 | DOI: 10.1002/bit.24804

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      A monoclonal DR4-CFP/YFP FRET reporter cell line was developed to profile the dynamic activation of TRAIL–DR4 in live cells in real-time for anti-cancer drug screening. Confocal imaging revealed that a majority of DR4-CFP and DR4-YFP resided on cell membranes with a great degree of colocalization. Using the YFP photobleaching method, the FRET efficiency upon TRAIL stimulations was 9% or 27% when an analysis was performed over a whole cell or around cell membranes, respectively.

    14. Engineering Science of Biological Systems

      Homogenization of Pseudomonas aeruginosa PAO1 biofilms visualized by freeze-substitution electron microscopy (pages 1405–1418)

      T. Guélon, R.C. Hunter, J.D. Mathias and G. Deffuant

      Version of Record online: 17 JAN 2013 | DOI: 10.1002/bit.24805

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      The main contribution of this article is to determine the influence of the spatial distribution of bacteria on the mechanical properties of bacterial biofilms. For this purpose, homogenization techniques are used to investigate freeze subtitution electron micrographs of biofilm cross-sections. The results demonstrate significant heterogeneities in terms of mechanical properties and give new understanding about the detachment process.

    15. Synthetic Biology

      Orthogonal control of endogenous gene expression in mammalian cells using synthetic ligands (pages 1419–1429)

      Jing Liang, Michael J. McLachlan and Huimin Zhao

      Version of Record online: 15 JAN 2013 | DOI: 10.1002/bit.24807

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      The authors report the development and characterization of a ligand controlled gene switch that activates endogenous VEGF-A expression in HEK293 cells by more than 100-fold in the presence of 4,4′-dyhydroxybenzil (DHB), a small molecule, non-steroid synthetic ligand, which acts orthogonally in a mammalian system. The system has the flexibility to allow for the control of any mammalian gene and of multiple genes simultaneously or orthogonally.

    16. Tissue Engineering and Delivery Systems

      Biomimetic injectable HUVEC-adipocytes/collagen/alginate microsphere co-cultures for adipose tissue engineering (pages 1430–1443)

      Rui Yao, Renji Zhang, Feng Lin and Jie Luan

      Version of Record online: 27 DEC 2012 | DOI: 10.1002/bit.24784

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      Biomimetic microtissues composed of surface-coated adipocyte/collagen/alginate microspheres and HUVECs co-cultures were developed in this paper. These co-cultures contained both a tissue element and a vascularization element and highly resembled the components, distribution and structure of natural adipose tissue. Subcutaneous injection into the node mice suggested vascularized adipose tissue formation with functional anastomosis and long-term stability of volume and weight, indicating that the vasculature formed within the constructs benefited the formation, maturity and maintenance of adipose tissue.

    17. A new method of fabricating robust freeform 3D ceramic scaffolds for bone tissue regeneration (pages 1444–1455)

      Young-Joon Seol, Dong Yong Park, Ju Young Park, Sung Won Kim, Seong Jin Park and Dong-Woo Cho

      Version of Record online: 15 JAN 2013 | DOI: 10.1002/bit.24794

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      Robust ceramic scaffolds, which have a desired architecture, were successfully fabricated by projection-based microstereolithography, and dilatometric analysis was conducted to determine the sintering temperature. The mechanical properties of the ceramic scaffolds were improved by infiltrating them with a polycaprolactone solution. Furthermore, the osteogenic gene expression on ceramic/polymer scaffolds was better than that on the ceramic scaffolds.

    18. Pharmacokinetics and brain uptake in the rhesus monkey of a fusion protein of arylsulfatase a and a monoclonal antibody against the human insulin receptor (pages 1456–1465)

      Ruben J. Boado, Jeff Zhiqiang Lu, Eric K.-W. Hui, Rachita K. Sumbria and William M. Pardridge

      Version of Record online: 25 DEC 2012 | DOI: 10.1002/bit.24795

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      Targeted-delivery of the lysosomal enzyme, arylsulfatase A (ASA), across the blood-brain barrier (BBB) for treatment of the brain in metachromatic leukodystrophy is possible following the re-engineering of the enzyme as an IgG-enzyme fusion protein. The IgG domain of the fusion protein is a genetically engineered monoclonal antibody (MAb) against the human insulin receptor (HIR). The monoclonal antibody acts as a molecular Trojan horse to ferry the enzyme into brain via transport on the endogenous BBB insulin receptor.

    19. Combined effects of direct current stimulation and immobilized BMP-2 for enhancement of osteogenesis (pages 1466–1475)

      Jieyu Zhang, Koon Gee Neoh, Xuefeng Hu, En-Tang Kang and Wilson Wang

      Version of Record online: 29 DEC 2012 | DOI: 10.1002/bit.24796

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      Electrical stimulation (ES) can accelerate bone fracture healing, but the implanted metal electrodes may cause adverse effects. Herein, the authors propose a strategy to replace the metal electrodes with a biodegradable, electrically conductive film comprising polypyrrole nanoparticles and chitosan, and functionalized with bone morphogenetic protein-2 (BMP-2). Osteoblasts cultured on this BMP-2-functionalized film and subjected to ES exhibited a twofold increase in mineralization over the control group (i.e., without immobilized BMP-2 and ES) after 21 days.

    20. Engineering superficial zone features in tissue engineered cartilage (pages 1476–1486)

      Tony Chen, Matthew J. Hilton, Edward B. Brown, Michael J. Zuscik and Hani A. Awad

      Version of Record online: 27 DEC 2012 | DOI: 10.1002/bit.24799

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      A major challenge in cartilage tissue engineering is reproducing the native extracellular matrix anisotropy. This study uses a hydrodynamic rotating bioreactor to mimic aspects of the flow fields produced during joint sliding and characterizes the effect of these hydrodynamic fields on the anisotropy of tissue engineered cartilage hydrogels and the production of surface zone specific matrix proteins and structural alignment.

    21. Brushite cement additives inhibit attachment to cell culture beads (pages 1487–1494)

      Parastoo Jamshidi, Rachel H. Bridson, Adrian J. Wright and Liam M. Grover

      Version of Record online: 17 JAN 2013 | DOI: 10.1002/bit.24806

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      The schematic below summarizes how post-processing of brushite cell culture beads enables cell attachment. Without immersion in physiologically relevant media, large scale cell detachment occurred following seeding.

    22. Programmable mechanical stimulation influences tendon homeostasis in a bioreactor system (pages 1495–1507)

      Tao Wang, Zhen Lin, Robert E. Day, Bruce Gardiner, Euphemie Landao-Bassonga, Jonas Rubenson, Thomas B. Kirk, David W. Smith, David G. Lloyd, Gerard Hardisty, Allan Wang, Qiujian Zheng and Ming H. Zheng

      Version of Record online: 4 FEB 2013 | DOI: 10.1002/bit.24809

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      The graph provides information related to matrix damage (black curve) and production (red broken curve) affected by mechanical stimulation. A zone indicates the small range of anabolic effect caused by mechanical stimulation. Matrix production stimulated by mechanical loading overcomes the matrix damage that the tendon is able to maintain its structural integrity. C zone indicates two catabolic zones that matrix damage caused by mechanical stretching overcomes the matrix production result in tendinopathy.

    23. Bioactive polyacrylamide hydrogels with gradients in mechanical stiffness (pages 1508–1519)

      Vincent E.G. Diederich, Peter Studer, Anita Kern, Marco Lattuada, Giuseppe Storti, Ram I. Sharma, Jess G. Snedeker and Massimo Morbidelli

      Version of Record online: 4 JAN 2013 | DOI: 10.1002/bit.24810

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      A technique for the preparation of polyacrylamide hydrogels with a gradient in Young's modulus from 150 kPa down to 20 kPa within a length of 10 mm, is presented. Upon surface treatment with collagen I, the produced hydrogels are bioactive and human foreskin fibroblasts feel the strength of the underlying material. After 2 hours, HFFs on the soft end of the sample are still round and small, while they are already well spread on the stiff end of the substrate.

  6. Communication to the Editor

    1. Top of page
    2. Cover
    3. Contents
    4. Spotlights
    5. Review
    6. Articles
    7. Communication to the Editor
    8. Errata
    1. Cellular and Metabolic Engineering

      Towards a metabolic engineering strain “commons”: An Escherichia coli platform strain for ethanol production (pages 1520–1526)

      Lauren B.A. Woodruff, Brian L. May, Joseph R. Warner and Ryan T. Gill

      Version of Record online: 29 JAN 2013 | DOI: 10.1002/bit.24840

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      Pichia pastoris has high alcohol oxidase activity and, although often directed at methanol metabolism, can non-specifically oxidize other alcohols, here benzyl alcohol to benzaldehyde, an important fragrance/flavor compound. Benzaldehyde strongly inhibited the biotransformation, however, and a two-phase partitioning bioreactor (TPPB) was employed using amorphous polymer beads to sequester the produced benzaldehyde. The uptake mechanism was confirmed to be by absorption, not adsorption, as is seen in non-selective materials such as activated carbon. The benzaldehyde volumetric productivity was double in the TPPB compared to single phase.

  7. Errata

    1. Top of page
    2. Cover
    3. Contents
    4. Spotlights
    5. Review
    6. Articles
    7. Communication to the Editor
    8. Errata
    1. Erratum

      You have free access to this content
      Erratam: Influence of the water activity of a solid substrate on the growth rate and sporogenesis of filamentous fungi (page 1527)

      P. Gervais, P. Molin, W. Grajek and M. Bensoussan

      Version of Record online: 12 FEB 2013 | DOI: 10.1002/bit.24811

      This article corrects:

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