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  Subjects -> BIOLOGY (Total: 3149 journals)
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    - BIOTECHNOLOGY (237 journals)
    - BOTANY (231 journals)
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BIOTECHNOLOGY (237 journals)                  1 2 | Last

Showing 1 - 200 of 237 Journals sorted alphabetically
3 Biotech     Open Access   (Followers: 8)
Advanced Biomedical Research     Open Access  
Advances in Bioscience and Biotechnology     Open Access   (Followers: 14)
Advances in Genetic Engineering & Biotechnology     Hybrid Journal   (Followers: 8)
African Journal of Biotechnology     Open Access   (Followers: 6)
Algal Research     Partially Free   (Followers: 10)
American Journal of Biochemistry and Biotechnology     Open Access   (Followers: 64)
American Journal of Bioinformatics Research     Open Access   (Followers: 7)
American Journal of Polymer Science     Open Access   (Followers: 31)
Anadolu University Journal of Science and Technology : C Life Sciences and Biotechnology     Open Access  
Animal Biotechnology     Hybrid Journal   (Followers: 8)
Annales des Sciences Agronomiques     Full-text available via subscription  
Applied Biochemistry and Biotechnology     Hybrid Journal   (Followers: 43)
Applied Bioenergy     Open Access  
Applied Biosafety     Hybrid Journal  
Applied Food Biotechnology     Open Access   (Followers: 3)
Applied Microbiology and Biotechnology     Hybrid Journal   (Followers: 63)
Applied Mycology and Biotechnology     Full-text available via subscription   (Followers: 4)
Arthroplasty Today     Open Access   (Followers: 1)
Artificial Cells, Nanomedicine and Biotechnology     Hybrid Journal   (Followers: 1)
Asia Pacific Biotech News     Hybrid Journal   (Followers: 2)
Asian Journal of Biotechnology     Open Access   (Followers: 8)
Asian Pacific Journal of Tropical Biomedicine     Open Access   (Followers: 2)
Australasian Biotechnology     Full-text available via subscription   (Followers: 1)
Banat's Journal of Biotechnology     Open Access  
BBR : Biochemistry and Biotechnology Reports     Open Access   (Followers: 5)
Bio-Algorithms and Med-Systems     Hybrid Journal   (Followers: 2)
Bio-Research     Full-text available via subscription   (Followers: 3)
Bioactive Materials     Open Access   (Followers: 1)
Biocatalysis and Agricultural Biotechnology     Hybrid Journal   (Followers: 4)
Biocybernetics and Biological Engineering     Full-text available via subscription   (Followers: 5)
Bioethics UPdate     Hybrid Journal  
Biofuels     Hybrid Journal   (Followers: 11)
Biofuels Engineering     Open Access   (Followers: 1)
Biological & Pharmaceutical Bulletin     Full-text available via subscription   (Followers: 4)
Biological Cybernetics     Hybrid Journal   (Followers: 10)
Biomarkers and Genomic Medicine     Open Access   (Followers: 3)
Biomarkers in Drug Development     Partially Free   (Followers: 1)
Biomaterials Research     Open Access   (Followers: 4)
BioMed Research International     Open Access   (Followers: 4)
Biomédica     Open Access  
Biomedical and Biotechnology Research Journal     Open Access  
Biomedical Engineering Research     Open Access   (Followers: 6)
Biomedical glasses     Open Access  
Biomedical Reports     Full-text available via subscription  
BioMedicine     Open Access  
Biomedika     Open Access  
Bioprinting     Hybrid Journal   (Followers: 1)
Bioresource Technology Reports     Hybrid Journal   (Followers: 1)
Bioscience, Biotechnology, and Biochemistry     Hybrid Journal   (Followers: 21)
Biosimilars     Open Access   (Followers: 1)
Biosurface and Biotribology     Open Access  
Biotechnic and Histochemistry     Hybrid Journal   (Followers: 2)
BioTechniques : The International Journal of Life Science Methods     Full-text available via subscription   (Followers: 28)
Biotechnologia Acta     Open Access   (Followers: 1)
Biotechnologie, Agronomie, Société et Environnement     Open Access   (Followers: 2)
Biotechnology     Open Access   (Followers: 5)
Biotechnology & Biotechnological Equipment     Open Access   (Followers: 4)
Biotechnology Advances     Hybrid Journal   (Followers: 33)
Biotechnology and Applied Biochemistry     Hybrid Journal   (Followers: 44)
Biotechnology and Bioengineering     Hybrid Journal   (Followers: 155)
Biotechnology and Bioprocess Engineering     Hybrid Journal   (Followers: 5)
Biotechnology and Genetic Engineering Reviews     Hybrid Journal   (Followers: 13)
Biotechnology and Health Sciences     Open Access   (Followers: 1)
Biotechnology and Molecular Biology Reviews     Open Access   (Followers: 2)
Biotechnology Annual Review     Full-text available via subscription   (Followers: 5)
Biotechnology for Biofuels     Open Access   (Followers: 10)
Biotechnology Frontier     Open Access   (Followers: 2)
Biotechnology Journal     Hybrid Journal   (Followers: 16)
Biotechnology Law Report     Hybrid Journal   (Followers: 4)
Biotechnology Letters     Hybrid Journal   (Followers: 34)
Biotechnology Progress     Hybrid Journal   (Followers: 39)
Biotechnology Reports     Open Access  
Biotechnology Research International     Open Access   (Followers: 1)
Biotechnology Techniques     Hybrid Journal   (Followers: 10)
Biotecnología Aplicada     Open Access  
Bioteknologi (Biotechnological Studies)     Open Access  
Biotribology     Hybrid Journal   (Followers: 1)
BMC Biotechnology     Open Access   (Followers: 16)
Cell Biology and Development     Open Access  
Chinese Journal of Agricultural Biotechnology     Full-text available via subscription   (Followers: 4)
Communications in Mathematical Biology and Neuroscience     Open Access  
Computational and Structural Biotechnology Journal     Open Access   (Followers: 2)
Computer Methods and Programs in Biomedicine     Hybrid Journal   (Followers: 8)
Contributions to Tobacco Research     Open Access   (Followers: 2)
Copernican Letters     Open Access   (Followers: 1)
Critical Reviews in Biotechnology     Hybrid Journal   (Followers: 20)
Crop Breeding and Applied Biotechnology     Open Access   (Followers: 3)
Current Bionanotechnology     Hybrid Journal  
Current Biotechnology     Hybrid Journal   (Followers: 4)
Current Opinion in Biomedical Engineering     Hybrid Journal   (Followers: 1)
Current Opinion in Biotechnology     Hybrid Journal   (Followers: 56)
Current Pharmaceutical Biotechnology     Hybrid Journal   (Followers: 9)
Current Research in Bioinformatics     Open Access   (Followers: 12)
Current Trends in Biotechnology and Chemical Research     Open Access   (Followers: 3)
Current trends in Biotechnology and Pharmacy     Open Access   (Followers: 8)
EBioMedicine     Open Access  
Electronic Journal of Biotechnology     Open Access  
Entomologia Generalis     Full-text available via subscription  
Environmental Science : Processes & Impacts     Full-text available via subscription   (Followers: 4)
Experimental Biology and Medicine     Hybrid Journal   (Followers: 3)
Folia Medica Indonesiana     Open Access  
Food Bioscience     Hybrid Journal  
Food Biotechnology     Hybrid Journal   (Followers: 9)
Food Science and Biotechnology     Hybrid Journal   (Followers: 8)
Frontiers in Bioengineering and Biotechnology     Open Access   (Followers: 6)
Frontiers in Systems Biology     Open Access   (Followers: 2)
Fungal Biology and Biotechnology     Open Access   (Followers: 2)
GM Crops and Food: Biotechnology in Agriculture and the Food Chain     Full-text available via subscription   (Followers: 1)
GSTF Journal of BioSciences     Open Access  
HAYATI Journal of Biosciences     Open Access  
Horticulture, Environment, and Biotechnology     Hybrid Journal   (Followers: 11)
IEEE Transactions on Molecular, Biological and Multi-Scale Communications     Hybrid Journal   (Followers: 1)
IET Nanobiotechnology     Hybrid Journal   (Followers: 2)
IIOAB Letters     Open Access  
IN VIVO     Full-text available via subscription   (Followers: 4)
Indian Journal of Biotechnology (IJBT)     Open Access   (Followers: 2)
Indonesia Journal of Biomedical Science     Open Access   (Followers: 2)
Indonesian Journal of Biotechnology     Open Access   (Followers: 1)
Industrial Biotechnology     Hybrid Journal   (Followers: 18)
International Biomechanics     Open Access  
International Journal of Bioinformatics Research and Applications     Hybrid Journal   (Followers: 13)
International Journal of Biomechatronics and Biomedical Robotics     Hybrid Journal   (Followers: 4)
International Journal of Biomedical Research     Open Access   (Followers: 2)
International Journal of Biotechnology     Hybrid Journal   (Followers: 5)
International Journal of Biotechnology and Molecular Biology Research     Open Access   (Followers: 3)
International Journal of Biotechnology for Wellness Industries     Partially Free   (Followers: 1)
International Journal of Environment, Agriculture and Biotechnology     Open Access   (Followers: 5)
International Journal of Functional Informatics and Personalised Medicine     Hybrid Journal   (Followers: 4)
International Journal of Medicine and Biomedical Research     Open Access   (Followers: 1)
International Journal of Nanotechnology and Molecular Computation     Full-text available via subscription   (Followers: 3)
International Journal of Radiation Biology     Hybrid Journal   (Followers: 4)
Iranian Journal of Biotechnology     Open Access  
ISABB Journal of Biotechnology and Bioinformatics     Open Access  
Italian Journal of Food Science     Open Access   (Followers: 1)
Journal of Biometrics & Biostatistics     Open Access   (Followers: 3)
Journal of Bioterrorism & Biodefense     Open Access   (Followers: 6)
Journal of Petroleum & Environmental Biotechnology     Open Access   (Followers: 1)
Journal of Advanced Therapies and Medical Innovation Sciences     Open Access  
Journal of Advances in Biotechnology     Open Access   (Followers: 5)
Journal Of Agrobiotechnology     Open Access  
Journal of Analytical & Bioanalytical Techniques     Open Access   (Followers: 7)
Journal of Animal Science and Biotechnology     Open Access   (Followers: 4)
Journal of Applied Biomedicine     Open Access   (Followers: 2)
Journal of Applied Biotechnology     Open Access   (Followers: 2)
Journal of Applied Biotechnology Reports     Open Access   (Followers: 2)
Journal of Applied Mathematics & Bioinformatics     Open Access   (Followers: 5)
Journal of Biologically Active Products from Nature     Hybrid Journal   (Followers: 1)
Journal of Biomaterials and Nanobiotechnology     Open Access   (Followers: 6)
Journal of Biomedical Photonics & Engineering     Open Access  
Journal of Biomedical Practitioners     Open Access  
Journal of Bioprocess Engineering and Biorefinery     Full-text available via subscription  
Journal of Bioprocessing & Biotechniques     Open Access  
Journal of Biosecurity, Biosafety and Biodefense Law     Hybrid Journal   (Followers: 3)
Journal of Biotechnology     Hybrid Journal   (Followers: 68)
Journal of Biotechnology and Strategic Health Research     Open Access  
Journal of Chemical and Biological Interfaces     Full-text available via subscription   (Followers: 1)
Journal of Chemical Technology & Biotechnology     Hybrid Journal   (Followers: 9)
Journal of Chitin and Chitosan Science     Full-text available via subscription  
Journal of Colloid Science and Biotechnology     Full-text available via subscription  
Journal of Commercial Biotechnology     Full-text available via subscription   (Followers: 6)
Journal of Crop Science and Biotechnology     Hybrid Journal   (Followers: 3)
Journal of Essential Oil Research     Hybrid Journal   (Followers: 2)
Journal of Experimental Biology     Full-text available via subscription   (Followers: 24)
Journal of Genetic Engineering and Biotechnology     Open Access   (Followers: 5)
Journal of Ginseng Research     Open Access  
Journal of Industrial Microbiology and Biotechnology     Hybrid Journal   (Followers: 16)
Journal of Integrative Bioinformatics     Open Access  
Journal of International Biotechnology Law     Hybrid Journal   (Followers: 3)
Journal of Medical Imaging and Health Informatics     Full-text available via subscription  
Journal of Molecular Biology and Biotechnology     Open Access  
Journal of Molecular Microbiology and Biotechnology     Full-text available via subscription   (Followers: 11)
Journal of Nano Education     Full-text available via subscription  
Journal of Nanobiotechnology     Open Access   (Followers: 4)
Journal of Nanofluids     Full-text available via subscription   (Followers: 1)
Journal of Organic and Biomolecular Simulations     Open Access  
Journal of Plant Biochemistry and Biotechnology     Hybrid Journal   (Followers: 4)
Journal of Science and Applications : Biomedicine     Open Access  
Journal of the Mechanical Behavior of Biomedical Materials     Hybrid Journal   (Followers: 11)
Journal of Trace Elements in Medicine and Biology     Hybrid Journal   (Followers: 1)
Journal of Tropical Microbiology and Biotechnology     Full-text available via subscription  
Journal of Yeast and Fungal Research     Open Access   (Followers: 1)
Marine Biotechnology     Hybrid Journal   (Followers: 4)
Messenger     Full-text available via subscription  
Metabolic Engineering Communications     Open Access   (Followers: 4)
Metalloproteinases In Medicine     Open Access  
Microalgae Biotechnology     Open Access   (Followers: 2)
Microbial Biotechnology     Open Access   (Followers: 9)
MicroMedicine     Open Access   (Followers: 3)
Molecular and Cellular Biomedical Sciences     Open Access  
Molecular Biotechnology     Hybrid Journal   (Followers: 13)
Molecular Genetics and Metabolism Reports     Open Access   (Followers: 3)
Nanobiomedicine     Open Access  
Nanobiotechnology     Hybrid Journal   (Followers: 2)
Nanomaterials and Nanotechnology     Open Access  
Nanomaterials and Tissue Regeneration     Open Access  
Nanomedicine and Nanobiology     Full-text available via subscription  
Nanomedicine Research Journal     Open Access  
Nanotechnology Reviews     Hybrid Journal   (Followers: 5)
Nature Biotechnology     Full-text available via subscription   (Followers: 535)

        1 2 | Last

Journal Cover
Current Opinion in Biotechnology
Journal Prestige (SJR): 3.202
Citation Impact (citeScore): 8
Number of Followers: 56  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0958-1669
Published by Elsevier Homepage  [3163 journals]
  • Integrating bioinformatics approaches for a comprehensive interpretation
           of metabolomics datasets
    • Authors: Dinesh Kumar Barupal; Sili Fan; Oliver Fiehn
      Pages: 1 - 9
      Abstract: Publication date: December 2018
      Source:Current Opinion in Biotechnology, Volume 54
      Author(s): Dinesh Kumar Barupal, Sili Fan, Oliver Fiehn
      Access to high quality metabolomics data has become a routine component for biological studies. However, interpreting those datasets in biological contexts remains a challenge, especially because many identified metabolites are not found in biochemical pathway databases. Starting from statistical analyses, a range of new tools are available, including metabolite set enrichment analysis, pathway and network visualization, pathway prediction, biochemical databases and text mining. Integrating these approaches into comprehensive and unbiased interpretations must carefully consider both caveats of the metabolomics dataset itself as well as the structure and properties of the biological study design. Special considerations need to be taken when adopting approaches from genomics for use in metabolomics. R and Python programming language are enabling an easier exchange of diverse tools to deploy integrated workflows. This review summarizes the key ideas and latest developments in regards to these approaches.
      Graphical abstract image

      PubDate: 2018-02-15T10:39:38Z
      DOI: 10.1016/j.copbio.2018.01.010
      Issue No: Vol. 54 (2018)
       
  • Advances in computational metabolomics and databases deepen the
           understanding of metabolisms
    • Authors: Hiroshi Tsugawa
      Pages: 10 - 17
      Abstract: Publication date: December 2018
      Source:Current Opinion in Biotechnology, Volume 54
      Author(s): Hiroshi Tsugawa
      Mass spectrometry (MS)-based metabolomics is the popular platform for metabolome analyses. Computational techniques for the processing of MS raw data, for example, feature detection, peak alignment, and the exclusion of false-positive peaks, have been established. The next stage of untargeted metabolomics would be to decipher the mass fragmentation of small molecules for the global identification of human-, animal-, plant-, and microbiota metabolomes, resulting in a deeper understanding of metabolisms. This review is an update on the latest computational metabolomics including known/expected structure databases, chemical ontology classifications, and mass spectrometry cheminformatics for the interpretation of mass fragmentations and for the elucidation of unknown metabolites. The importance of metabolome ‘databases’ and ‘repositories’ is also discussed because novel biological discoveries are often attributable to the accumulation of data, to relational databases, and to their statistics. Lastly, a practical guide for metabolite annotations is presented as the summary of this review.
      Graphical abstract image

      PubDate: 2018-02-15T10:39:38Z
      DOI: 10.1016/j.copbio.2018.01.008
      Issue No: Vol. 54 (2018)
       
  • Design and optimization of genetically encoded biosensors for
           high-throughput screening of chemicals
    • Authors: Hyun Gyu Lim; Sungho Jang; Sungyeon Jang; Sang Woo Seo; Gyoo Yeol Jung
      Pages: 18 - 25
      Abstract: Publication date: December 2018
      Source:Current Opinion in Biotechnology, Volume 54
      Author(s): Hyun Gyu Lim, Sungho Jang, Sungyeon Jang, Sang Woo Seo, Gyoo Yeol Jung
      Evolutionary engineering of microbes for the production of metabolites requires efficient screening methods to test vast mutant libraries. Genetically encoded biosensors are regarded as promising screening devices owing to their wide range of detectable ligands and great applicability to high-throughput screening and selection. Here, we reviewed the current progress in design and optimization of biosensors for high-throughput screening of chemicals. First, we summarized genetic parts of biosensors and strategies for their discovery and development. Next, we explained the properties of biosensors that are relevant to high-throughput screening. Finally, we described various methods for tuning biosensors to fulfill requirements of an efficient screening.
      Graphical abstract image

      PubDate: 2018-02-05T10:32:07Z
      DOI: 10.1016/j.copbio.2018.01.011
      Issue No: Vol. 54 (2018)
       
  • Exploiting transcriptomic data for metabolic engineering: toward a
           systematic strain design
    • Authors: Minsuk Kim; Beom Gi Park; Joonwon Kim; Jin Young Kim; Byung-Gee Kim
      Pages: 26 - 32
      Abstract: Publication date: December 2018
      Source:Current Opinion in Biotechnology, Volume 54
      Author(s): Minsuk Kim, Beom Gi Park, Joonwon Kim, Jin Young Kim, Byung-Gee Kim
      Transcriptomics is now recognized as a primary tool for metabolic engineering as it can be used for identifying new strain designs by diagnosing current states of microbial cells. This review summarizes current application of transcriptomic data for strain design. Along with a few successful examples, limitations of conventionally used differentially expressed gene-based strain design approaches have been discussed, which have been major reasons why transcriptomic data are considerably underutilized. Recently, integrative network-based approaches interpreting transcriptomic data in the context of biological networks were invented to provide complimentary solutions for metabolic engineering by overcoming the limitations of conventional approaches. Here, we highlight recent pioneering studies in which integrative network-based methods have been used for providing novel strain designs.

      PubDate: 2018-02-15T10:39:38Z
      DOI: 10.1016/j.copbio.2018.01.020
      Issue No: Vol. 54 (2018)
       
  • Advances in analytical tools for high throughput strain engineering
    • Authors: Esteban Marcellin; Lars Keld Nielsen
      Pages: 33 - 40
      Abstract: Publication date: December 2018
      Source:Current Opinion in Biotechnology, Volume 54
      Author(s): Esteban Marcellin, Lars Keld Nielsen
      The emergence of inexpensive, base-perfect genome editing is revolutionising biology. Modern industrial biotechnology exploits the advances in genome editing in combination with automation, analytics and data integration to build high-throughput automated strain engineering pipelines also known as biofoundries. Biofoundries replace the slow and inconsistent artisanal processes used to build microbial cell factories with an automated design–build–test cycle, considerably reducing the time needed to deliver commercially viable strains. Testing and hence learning remains relatively shallow, but recent advances in analytical chemistry promise to increase the depth of characterization possible. Analytics combined with models of cellular physiology in automated systems biology pipelines should enable deeper learning and hence a steeper pitch of the learning cycle. This review explores the progress, advances and remaining bottlenecks of analytical tools for high throughput strain engineering.
      Graphical abstract image

      PubDate: 2018-02-15T10:39:38Z
      DOI: 10.1016/j.copbio.2018.01.027
      Issue No: Vol. 54 (2018)
       
  • Designing artificial metabolic pathways, construction of target enzymes,
           and analysis of their function
    • Authors: Yutaro Mori; Tomokazu Shirai
      Pages: 41 - 44
      Abstract: Publication date: December 2018
      Source:Current Opinion in Biotechnology, Volume 54
      Author(s): Yutaro Mori, Tomokazu Shirai
      Artificial design of metabolic pathways is essential for the production of useful compounds using microbes. Based on this design, heterogeneous genes are introduced into the host, and then various analysis and evaluation methods are conducted to ensure that the target enzyme reactions are functionalized within the cell. In this chapter, we list successful examples of useful compounds produced by designing artificial metabolic pathways, and describe the methods involved in analyzing, evaluating, and optimizing the target enzyme reaction.
      Graphical abstract image

      PubDate: 2018-02-25T19:18:08Z
      DOI: 10.1016/j.copbio.2018.01.021
      Issue No: Vol. 54 (2018)
       
  • Toward prediction and control of antibiotic-resistance evolution
    • Authors: Chikara Furusawa; Takaaki Horinouchi; Tomoya Maeda
      Pages: 45 - 49
      Abstract: Publication date: December 2018
      Source:Current Opinion in Biotechnology, Volume 54
      Author(s): Chikara Furusawa, Takaaki Horinouchi, Tomoya Maeda
      The emergence of antibiotic-resistant bacteria is a serious public concern. To deal with this problem, recent advances in technology and the use of laboratory evolution experiments have provided valuable information on the phenotypic and genotypic changes that occur during the evolution of resistance. These studies have demonstrated the existence of evolutionary constraints on the development of drug-resistance, which suggests predictability in its evolution. In this review, we focus on the possibility to predict and control the evolution of antibiotic resistance, based on quantitative analysis of phenotypic and genotypic changes observed in bacterial laboratory evolution. We emphasize the key challenges in evolutionary biology that will contribute to the development of appropriate treatment strategies for preventing resistance evolution.

      PubDate: 2018-02-15T10:39:38Z
      DOI: 10.1016/j.copbio.2018.01.026
      Issue No: Vol. 54 (2018)
       
  • Energy transfer and distribution in photosystem super/megacomplexes of
           plants
    • Authors: Makio Yokono; Seiji Akimoto
      Pages: 50 - 56
      Abstract: Publication date: December 2018
      Source:Current Opinion in Biotechnology, Volume 54
      Author(s): Makio Yokono, Seiji Akimoto
      Traditionally, two types of photosystem reaction centers (PSI and PSII) are thought to be spatially dispersed in the plant thylakoid membrane. In this model, PSI and PSII independently accept excitation energy from their own peripheral light-harvesting complexes, LHCI and LHCII, respectively, and form supercomplexes (PSI–LHCI and PSII–LHCII). However, recent studies using a combination of mild detergent treatment and spectroscopic analysis have revealed the existence of various megacomplexes such as a PSI–PSII megacomplex and a PSII megacomplex. Flexibility in the formation of supercomplexes and megacomplexes is important for land plants to regulate excitation energy to survive under strong and fluctuating sunlight on land.

      PubDate: 2018-02-25T19:18:08Z
      DOI: 10.1016/j.copbio.2018.01.001
      Issue No: Vol. 54 (2018)
       
  • Pharmacognosy in the digital era: shifting to contextualized metabolomics
    • Authors: Pierre-Marie Allard; Jonathan Bisson; Antonio Azzollini; Guido F Pauli; Geoffrey A Cordell; Jean-Luc Wolfender
      Pages: 57 - 64
      Abstract: Publication date: December 2018
      Source:Current Opinion in Biotechnology, Volume 54
      Author(s): Pierre-Marie Allard, Jonathan Bisson, Antonio Azzollini, Guido F Pauli, Geoffrey A Cordell, Jean-Luc Wolfender
      Humans have co-evolved alongside numerous other organisms, some having a profound effect on health and nutrition. As the earliest pharmaceutical subject, pharmacognosy has evolved into a meta-discipline devoted to natural biomedical agents and their functional properties. While the acquisition of expanding data volumes is ongoing, contextualization is lagging. Thus, we assert that the establishment of an integrated and open databases ecosystem will nurture the discipline. After proposing an epistemological framework of knowledge acquisition in pharmacognosy, this study focuses on recent computational and analytical approaches. It then elaborates on the flux of research data, where good practices could foster the implementation of more integrated systems, which will in turn help shaping the future of pharmacognosy and determine its constitutional societal relevance.
      Graphical abstract image

      PubDate: 2018-03-06T13:54:55Z
      DOI: 10.1016/j.copbio.2018.02.010
      Issue No: Vol. 54 (2018)
       
  • Proteomics of cyanobacteria: current horizons
    • Authors: Natalia Battchikova; Dorota Muth-Pawlak; Eva-Mari Aro
      Pages: 65 - 71
      Abstract: Publication date: December 2018
      Source:Current Opinion in Biotechnology, Volume 54
      Author(s): Natalia Battchikova, Dorota Muth-Pawlak, Eva-Mari Aro
      Application of proteomics has made a profound impact on the cyanobacterial research. It has not only provided a global identification of expressed proteins in cyanobacterial cells, but has also brought valuable insights into dynamics of cell responses to environmental challenges, regulation mechanisms, structure of protein complexes, compartmentalization, and other important biological questions. In this review, we highlight current trends in proteomics of cyanobacteria and bring to focus rising techniques which have a huge potential in expanding our knowledge about cyanobacterial proteins and in developing cyanobacteria-based biotechnological applications.
      Graphical abstract image

      PubDate: 2018-03-06T13:54:55Z
      DOI: 10.1016/j.copbio.2018.02.012
      Issue No: Vol. 54 (2018)
       
  • There's (still) plenty of room at the bottom
    • Authors: Noah Olsman; Lea Goentoro
      Pages: 72 - 79
      Abstract: Publication date: December 2018
      Source:Current Opinion in Biotechnology, Volume 54
      Author(s): Noah Olsman, Lea Goentoro
      Motifs, circuits, and networks are core conceptual elements in modern systems and synthetic biology. While there are still undoubtedly more fascinating computations to discover at network level, there are also rich computations that we are only beginning to uncover within the diverse molecules that constitute the networks. Here we explore some work, both new and old, that showcases the incredible computational capacity of seemingly simple molecular mechanisms. A more sophisticated understanding of computations at the molecular level will inspire the development of a more nuanced toolbox for future biological engineering.
      Graphical abstract image Highlights

      PubDate: 2018-03-19T07:01:26Z
      DOI: 10.1016/j.copbio.2018.01.029
      Issue No: Vol. 54 (2018)
       
  • Isotopically nonstationary metabolic flux analysis (INST-MFA): putting
           theory into practice
    • Authors: Yi Ern Cheah; Jamey D Young
      Pages: 80 - 87
      Abstract: Publication date: December 2018
      Source:Current Opinion in Biotechnology, Volume 54
      Author(s): Yi Ern Cheah, Jamey D Young
      Typically, 13C flux analysis relies on assumptions of both metabolic and isotopic steady state. If metabolism is steady but isotope labeling is not allowed to fully equilibrate, isotopically nonstationary metabolic flux analysis (INST-MFA) can be used to estimate fluxes. This requires solution of differential equations that describe the time-dependent labeling of network metabolites, while iteratively adjusting the flux and pool size parameters to match the transient labeling measurements. INST-MFA holds a number of unique advantages over approaches that rely solely upon steady-state isotope enrichments. First, INST-MFA can be applied to estimate fluxes in autotrophic systems, which consume only single-carbon substrates. Second, INST-MFA is ideally suited to systems that label slowly due to the presence of large intermediate pools or pathway bottlenecks. Finally, INST-MFA provides increased measurement sensitivity to estimate reversible exchange fluxes and metabolite pool sizes, which represents a potential framework for integrating metabolomic analysis with 13C flux analysis. This review highlights the unique capabilities of INST-MFA, describes newly available software tools that automate INST-MFA calculations, presents several practical examples of recent INST-MFA applications, and discusses the technical challenges that lie ahead.

      PubDate: 2018-03-06T13:54:55Z
      DOI: 10.1016/j.copbio.2018.02.013
      Issue No: Vol. 54 (2018)
       
  • The promise of targeted proteomics for quantitative network biology
    • Authors: Masaki Matsumoto; Keiichi I Nakayama
      Pages: 88 - 97
      Abstract: Publication date: December 2018
      Source:Current Opinion in Biotechnology, Volume 54
      Author(s): Masaki Matsumoto, Keiichi I Nakayama
      Proteomics is a powerful tool for obtaining information on a large number of proteins with regard to their expression levels, interactions with other molecules, and posttranslational modifications. Whereas nontargeted, discovery proteomics uncovers differences in the proteomic landscape under different conditions, targeted proteomics has been developed to overcome the limitations of this approach with regard to quantitation. In addition to technical advances in instruments and informatics tools, the advent of the synthetic proteome composed of synthetic peptides or recombinant proteins has advanced the adoption of targeted proteomics across a wide range of research fields. Targeted proteomics can now be applied to measurement of the dynamics of any proteins of interest under a variety of conditions as well as to estimation of the absolute abundance or stoichiometry of proteins in a given network. Multiplexed targeted proteomics assays of high reproducibility and accuracy can provide insight at the quantitative level into entire networks that govern biological phenomena or diseases. Such assays will establish a new paradigm for data-driven science.

      PubDate: 2018-03-19T07:01:26Z
      DOI: 10.1016/j.copbio.2018.02.014
      Issue No: Vol. 54 (2018)
       
  • Computational methods for analyzing genome-wide chromosome conformation
           capture data
    • Authors: Chiara Nicoletti; Mattia Forcato; Silvio Bicciato
      Pages: 98 - 105
      Abstract: Publication date: December 2018
      Source:Current Opinion in Biotechnology, Volume 54
      Author(s): Chiara Nicoletti, Mattia Forcato, Silvio Bicciato
      In all organisms, chromatin is packed to fulfil structural constraints and functional requirements. The hierarchical model of chromatin organization in the 3D nuclear space encompasses different topologies at diverse scale lengths, with chromosomes occupying distinct volumes, further organized in compartments, inside which the chromatin fibers fold into large domains and short-range loops. In the recent years, the combination of chromosome conformation capture (3C) techniques and high-throughput sequencing allowed probing chromatin spatial organization at the whole genome-scale. 3C-based methods produce enormous amounts of genomic data that are analyzed using ad-hoc computational procedures. Here, we review the common pipelines and methods for the analysis of genome-wide chromosome conformation capture data, highlighting recent developments in key steps for the identification of chromatin structures.
      Graphical abstract image

      PubDate: 2018-03-19T07:01:26Z
      DOI: 10.1016/j.copbio.2018.01.023
      Issue No: Vol. 54 (2018)
       
  • Nano-spectroscopic imaging of proteins with near-field scanning optical
           microscopy (NSOM)
    • Authors: Yang-Chun Yong; Yan-Zhai Wang; Jian-Jiang Zhong
      Pages: 106 - 113
      Abstract: Publication date: December 2018
      Source:Current Opinion in Biotechnology, Volume 54
      Author(s): Yang-Chun Yong, Yan-Zhai Wang, Jian-Jiang Zhong
      Understanding the hierarchical structure of proteins at their fundamental length scales is essential to get insights into their functions and roles in fundamental biological processes. Near-field scanning optical microscopy (NSOM), which overcomes the diffraction limits of conventional optics, provides a powerful analytical tool to image target proteins at nanoscale resolution. Especially, by combining NSOM with infrared (IR) or Raman spectroscopy, near-field nanospectroscopic imaging of a single protein is achieved. In this review, we present the recent technical progress of NSOM setup for nanospectroscopic imaging of proteins, and its application to nanospectroscopic analysis of protein structures is highlighted and critically reviewed. Finally, current challenges and perspectives on application of NSOM in emerging areas of industrial, environmental and medical biotechnology are discussed.
      Graphical abstract image

      PubDate: 2018-04-11T12:31:23Z
      DOI: 10.1016/j.copbio.2018.01.022
      Issue No: Vol. 54 (2018)
       
  • Metabolomics tools for the synthetic biology of natural products
    • Authors: Katherine A Hollywood; Kamila Schmidt; Eriko Takano; Rainer Breitling
      Pages: 114 - 120
      Abstract: Publication date: December 2018
      Source:Current Opinion in Biotechnology, Volume 54
      Author(s): Katherine A Hollywood, Kamila Schmidt, Eriko Takano, Rainer Breitling
      Metabolomics plays an increasingly central role within the Design–Build–Test cycle of synthetic biology, in particular in applications targeting the discovery, diversification and optimised production of a wide range of natural products. For example, improved methods for the online monitoring of chemical reactions accelerate data generation to be compatible with the rapid iterations and increasing library sizes of automated synthetic biology pipelines. Combinations of label-free metabolic profiling and 13C-based flux analysis lead to increased resolution in the identification of metabolic bottlenecks affecting product yield in engineered microbes. And molecular networking strategies drastically increase our ability to identify and characterise novel chemically complex biomolecules of interest in a diverse range of samples.
      Graphical abstract image

      PubDate: 2018-04-11T12:31:23Z
      DOI: 10.1016/j.copbio.2018.02.015
      Issue No: Vol. 54 (2018)
       
  • Quantitative measurements in single-cell analysis: towards scalability in
           microbial bioprocess development
    • Authors: Philipp Demling; Christoph Westerwalbesloh; Stephan Noack; Wolfgang Wiechert; Dietrich Kohlheyer
      Pages: 121 - 127
      Abstract: Publication date: December 2018
      Source:Current Opinion in Biotechnology, Volume 54
      Author(s): Philipp Demling, Christoph Westerwalbesloh, Stephan Noack, Wolfgang Wiechert, Dietrich Kohlheyer
      Single-cell analysis in microfluidic cultivation devices bears a great potential for the development and optimization of industrial bioprocesses. High parallelization allows running a large number of cultivation experiments simultaneously even under quick alteration of environmental conditions. For example, the impact of changes in media composition on cell growth during classical batch cultivation can be easily resolved. A missing link for the scalability of microfluidic experiments is, however, their complete characterization via conventional performance indicators such as product titer and productivity. While existing mass spectrometry technology is not yet sufficiently coupled with microfluidics, optical methods like enzymatic assays or fluorescence sensors are promising alternatives but require further improvement to generate quantitative measurements of extracellular metabolites.
      Graphical abstract image

      PubDate: 2018-04-11T12:31:23Z
      DOI: 10.1016/j.copbio.2018.01.024
      Issue No: Vol. 54 (2018)
       
  • Non-protein biologic therapeutics
    • Authors: Susan T Sharfstein
      Pages: 65 - 75
      Abstract: Publication date: October 2018
      Source:Current Opinion in Biotechnology, Volume 53
      Author(s): Susan T Sharfstein
      While the therapeutic biologics are dominated by therapeutic proteins, particularly monoclonal antibodies, a wide range of non-protein therapeutic biologics are rapidly gaining ground both in clinical studies and approved products. Many of these first-in-class therapies provide novel treatment modalities and address previously untreatable conditions or undruggable targets. In particular, novel treatments for rare genetic disorders and qualitatively different oncology therapeutics have been approved in the last two years. This review discusses recent advances in peptide, nucleic acid, carbohydrate, vaccine, and cell-based therapies as well as the manufacturing and commercialization challenges associated with these novel therapeutics.
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      PubDate: 2018-01-03T23:13:33Z
      DOI: 10.1016/j.copbio.2017.12.014
      Issue No: Vol. 53 (2018)
       
  • Continuous integrated manufacturing of therapeutic proteins
    • Authors: Daniel Johannes Karst; Fabian Steinebach; Massimo Morbidelli
      Pages: 76 - 84
      Abstract: Publication date: October 2018
      Source:Current Opinion in Biotechnology, Volume 53
      Author(s): Daniel Johannes Karst, Fabian Steinebach, Massimo Morbidelli
      With the growth of our understanding of biopharmaceutical processes, a transition from classical batch to continuous integrated manufacturing of therapeutic proteins is taking place across laboratory, clinical and commercial scales. Encouraged by regulatory authorities, this transition is favoured by new emerging technologies as well as by the development of better simulation models. The current status of continuous cell culture and downstream processes and requirements for their successful integration are discussed in this article, with specific reference to product quality attributes.
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      PubDate: 2018-01-10T06:37:21Z
      DOI: 10.1016/j.copbio.2017.12.015
      Issue No: Vol. 53 (2018)
       
  • The road to animal-free glycosaminoglycan production: current efforts and
           bottlenecks
    • Authors: Abinaya Badri; Asher Williams; Robert J Linhardt; Mattheos AG Koffas
      Pages: 85 - 92
      Abstract: Publication date: October 2018
      Source:Current Opinion in Biotechnology, Volume 53
      Author(s): Abinaya Badri, Asher Williams, Robert J Linhardt, Mattheos AG Koffas
      Animal-extraction, despite its limitations, continues to monopolize the fast-growing glycosaminoglycan (GAG) industry. The past few years have seen an increased interest in the development of alternative GAG production methods. Chemical and chemo-enzymatic synthesis and biosynthesis from GAG producing cells, including engineered recombinant strains, are currently under investigation. Despite achieving considerable successes, these alternate approaches cannot yet meet worldwide demands for these important polysaccharides. Bottlenecks associated with achieving high-titers need to be addressed using newly developed tools. Several parameters including chassis choice, analytics, intracellular precursor synthesis, enzyme engineering and use of synthetic biology tools need to be optimized. We envision that new engineering approaches together with advances in the basic biology and chemistry of GAGs will move GAG production beyond its currently limited supply chain.
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      PubDate: 2018-01-10T06:37:21Z
      DOI: 10.1016/j.copbio.2017.12.018
      Issue No: Vol. 53 (2018)
       
  • Improving the success and impact of the metabolic engineering design,
           build, test, learn cycle by addressing proteins of unknown function
    • Authors: Laura R Jarboe
      Pages: 93 - 98
      Abstract: Publication date: October 2018
      Source:Current Opinion in Biotechnology, Volume 53
      Author(s): Laura R Jarboe
      Rational, predictive metabolic engineering of organisms requires an ability to associate biological activity to the corresponding gene(s). Despite extensive advances in the 20 years since the Escherichia coli genome was published, there are still gaps in our knowledge of protein function. The substantial amount of data that has been published, such as: omics-level characterization in a myriad of conditions; genome-scale libraries; and evolution and genome sequencing, provide means of identifying and prioritizing proteins for characterization. This review describes the scale of this knowledge gap, demonstrates the benefit of addressing the knowledge gap, and demonstrates the availability of interesting candidates for characterization.
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      PubDate: 2018-01-10T06:37:21Z
      DOI: 10.1016/j.copbio.2017.12.017
      Issue No: Vol. 53 (2018)
       
  • Role of raw materials in biopharmaceutical manufacturing: risk analysis
           and fingerprinting
    • Authors: Anurag S Rathore; Deepak Kumar; Nikhil Kateja
      Pages: 99 - 105
      Abstract: Publication date: October 2018
      Source:Current Opinion in Biotechnology, Volume 53
      Author(s): Anurag S Rathore, Deepak Kumar, Nikhil Kateja
      Accurate fingerprinting of critical raw materials that have significant impact on process performance and product quality is a necessary precursor for implementation of QbD in process and product development. This article presents a review of major developments in this space in the last 10 years, with a special emphasis on those in last 5 years. A step by step approach for managing raw materials in the QbD paradigm has been proposed. We think that it is necessary for the biotech industry to better manage variability originating from raw materials if holistic implementation of QbD is to be achieved.

      PubDate: 2018-01-10T06:37:21Z
      DOI: 10.1016/j.copbio.2017.12.022
      Issue No: Vol. 53 (2018)
       
  • In vivo catalyzed new-to-nature reactions
    • Authors: Johannes G Rebelein; Thomas R Ward
      Pages: 106 - 114
      Abstract: Publication date: October 2018
      Source:Current Opinion in Biotechnology, Volume 53
      Author(s): Johannes G Rebelein, Thomas R Ward
      Bioorthogonal chemistry largely relies on the use of abiotic metals to catalyze new-to-nature reactions in living systems. Over the past decade, metal complexes and metal-encapsulated systems such as nanoparticles have been developed to unravel the reactivity of transition metals, including ruthenium, palladium, iridium, copper, iron, and gold in biological systems. Thanks to these remarkable achievements, abiotic catalysts are able to fluorescently label cells, uncage or form cytotoxic drugs and activate enzymes in cellulo/vivo. Recently, strategies for the delivery of such catalysts to specific cell types, cell compartments or proteins were established. These studies reveal the enormous potential of this emerging field and its application in both medicinal chemistry and in synthetic biology.

      PubDate: 2018-01-10T06:37:21Z
      DOI: 10.1016/j.copbio.2017.12.008
      Issue No: Vol. 53 (2018)
       
  • The emerging impact of cell-free chemical biosynthesis
    • Authors: Kristen M Wilding; Song-Min Schinn; Emily A Long; Bradley C Bundy
      Pages: 115 - 121
      Abstract: Publication date: October 2018
      Source:Current Opinion in Biotechnology, Volume 53
      Author(s): Kristen M Wilding, Song-Min Schinn, Emily A Long, Bradley C Bundy
      Biomanufacturing has emerged as a promising alternative to chemocatalysis for green, renewable, complex synthesis of biofuels, medicines, and fine chemicals. Cell-free chemical biosynthesis offers additional advantages over in vivo production, enabling plug-and-play assembly of separately produced enzymes into an optimal cascade, versatile reaction conditions, and direct access to the reaction environment. In order for these advantages to be realized on the larger scale of industry, strategies are needed to reduce costs of biocatalyst generation, improve biocatalyst stability, and enable economically sustainable continuous cascade operation. Here we overview the advantages and remaining challenges of applying cell-free chemical biosynthesis for commodity production, and discuss recent advances in cascade engineering, enzyme immobilization, and enzyme encapsulation which constitute important steps towards addressing these challenges.
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      PubDate: 2018-01-10T06:37:21Z
      DOI: 10.1016/j.copbio.2017.12.019
      Issue No: Vol. 53 (2018)
       
  • Engineering yeast for utilization of alternative feedstocks
    • Authors: Allison Yaguchi; Michael Spagnuolo; Mark Blenner
      Pages: 122 - 129
      Abstract: Publication date: October 2018
      Source:Current Opinion in Biotechnology, Volume 53
      Author(s): Allison Yaguchi, Michael Spagnuolo, Mark Blenner
      Realizing the economic benefits of alternative substrates for commodity chemical bioproduction typically requires significant metabolic engineering of common model organisms, such as Saccharomyces cerevisiae. A growing toolkit is enabling engineering of non-conventional yeast that have robust native metabolism for xylose, acetate, aromatics, and waste lipids. Scheffersomyces stipitis was engineered to produce itaconic acid from xylose. Yarrowia lipolytica produced lipids from dilute acetate at over 100g/L. Cutaneotrichosporon oleaginosus was engineered to produce omega-3 fatty acids and recently was shown to accumulate nearly 70% lipids when grown on aromatics as a carbon source. Further improvement to toolkits for genetic engineering of non-conventional yeast will enable future development of alternative substrate conversion to biochemicals.
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      PubDate: 2018-01-25T16:34:22Z
      DOI: 10.1016/j.copbio.2017.12.003
      Issue No: Vol. 53 (2018)
       
  • Recent insights in microbial exopolysaccharide biosynthesis and
           engineering strategies
    • Authors: Jochen Schmid
      Pages: 130 - 136
      Abstract: Publication date: October 2018
      Source:Current Opinion in Biotechnology, Volume 53
      Author(s): Jochen Schmid
      The distinct biosynthesis pathways for microbial exopolysaccharide production provide different engineering strategies to tailor the chemical structures of the final polymers. This review focuses on the latest insights in the various pathways and identifies bottlenecks as well as promising targets for tailoring microbial polysaccharide production. The main engineering strategies includes the combinatorial assembly of glycosyltransferases and engineering of the Wzx and Wzy proteins for flipping of repeating units as well as polymerization. In the case of synthase based polysaccharides, the use of epimerases or engineering approaches of the synthase itself as well as overexpression of c-di-GMP levels is identified as one of the most promising strategies. For sucrase-based biosynthesis, the in vitro production by engineered sucrase enzymes or adjusted production conditions is shown as a very promising method.
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      PubDate: 2018-02-05T10:32:07Z
      DOI: 10.1016/j.copbio.2018.01.005
      Issue No: Vol. 53 (2018)
       
  • Integrated viral clearance strategies—reflecting on the present,
           projecting to the future
    • Authors: David J Roush
      Pages: 137 - 143
      Abstract: Publication date: October 2018
      Source:Current Opinion in Biotechnology, Volume 53
      Author(s): David J Roush
      Viral clearance and inactivation are critical steps in ensuring the safety of biological products derived from mammalian cell culture and are a component of an adventitious agent control strategy which spans both upstream and downstream processes. Although these approaches have been sufficient to support the development of biologics to date, the empirical and semi-quantitative nature of the approach leaves some potential gaps. For example, the concept of performing a quantitative risk assessment for the downstream components of virus safety was introduced in ICH Q5A for XMuLV. An ideal future state would be to perform a similar quantitative risk assessment for a range of viruses based on an assessment of potential virus risk in both upstream and downstream processes. This assessment combined with an integrated control strategy (including monitoring) would be extremely beneficial in minimizing potential adventitious agent risks. Significant progress has been achieved towards this goal in the last several years including recent advances in quantification of virus sequences in cell banks (ADVTIG), development of truly modular or generic viral clearance claims for specific unit operations, enhanced controls of upstream media (HTST/nanofiltration) and the use of RVLP for in-process monitoring. The recent shift towards continuous processing has the potential to enhance the criticality of in-line monitoring and the complexity of viral clearance and inactivation (owing to a wide range of potential ‘worst case’ viral clearance scenarios). However, gaps exist in, firstly, the ability to quantify potential virus risk levels in process streams in real-time, secondly, mechanistic understanding of virus/chromatography media interactions, and thirdly, mechanistic understanding of virus/filter interactions. Some new technologies may also need to be developed to allow for real-time confirmation of virus inactivation and clearance to support process development (both batch and continuous) and assessment of the impact of process deviations during manufacturing. This review paper provides an overview of the current state of an overall integrated control strategy for upstream and downstream processing and highlights the investments that could be pursued to achieve the future state of a quantitative virus risk assessment for a range of viruses. One potential approach to address these gaps is the use of data mining from large, comprehensive and diverse data sets to establish heuristic rules for virus detection, clearance and inactivation followed by specific hypothesis-driven experiments for cases that fall outside of the normal paradigm. Once this approach reaches a mature state suitable for implementation, there is an opportunity to update regulatory guidance (e.g. ICH Q5A) accordingly.

      PubDate: 2018-01-25T16:34:22Z
      DOI: 10.1016/j.copbio.2018.01.003
      Issue No: Vol. 53 (2018)
       
  • Applications of proteomic methods for CHO host cell protein
           characterization in biopharmaceutical manufacturing
    • Authors: Kristin N Valente; Nicholas E Levy; Kelvin H Lee; Abraham M Lenhoff
      Pages: 144 - 150
      Abstract: Publication date: October 2018
      Source:Current Opinion in Biotechnology, Volume 53
      Author(s): Kristin N Valente, Nicholas E Levy, Kelvin H Lee, Abraham M Lenhoff
      Chinese hamster ovary (CHO) cells are the most prevalent host organism for production of recombinant therapeutic proteins, including monoclonal antibodies (mAbs). Regulatory guidance mandates control of the host cell protein (HCP) concentration in the production process, which remains a primary challenge. Although HCP concentrations are typically measured by ELISA, orthogonal proteomic methods are gaining popularity for identification and quantitation of individual HCP species. Recent applications of proteomic techniques to characterize extracellular CHO HCPs include those that have explored the effects of upstream factors (cell line, viability, process conditions), characterized specific HCPs likely to co-purify by mAb interactions, identified HCPs likely to impact drug product quality, and enabled strategies to limit HCP expression (media composition, temperature shift, genetic modification) and maximize clearance (polishing chromatography, wash additives).

      PubDate: 2018-02-05T10:32:07Z
      DOI: 10.1016/j.copbio.2018.01.004
      Issue No: Vol. 53 (2018)
       
  • Debottlenecking protein secretion and reducing protein aggregation in the
           cellular host
    • Authors: Yizhou Zhou; Ravali Raju; Christina Alves; Alan Gilbert
      Pages: 151 - 157
      Abstract: Publication date: October 2018
      Source:Current Opinion in Biotechnology, Volume 53
      Author(s): Yizhou Zhou, Ravali Raju, Christina Alves, Alan Gilbert
      Chinese hamster ovary (CHO) cells have been extensively used for industrial production of biotherapeutics. With advances in cell line development and process optimization, production levels of therapeutic proteins using the CHO expression system have increased to beyond 10g per liter scale. These high-titer processes could challenge the secretory capacity of CHO cells, which can result in degradation and aggregation of the protein of interest. This review discusses bottlenecks in the secretory pathway of CHO cells that lead to inefficient secretion and aggregation of proteins, and summarizes current strategies to tackle these bottlenecks. In addition, emerging technologies that facilitate better understanding of cellular mechanisms in protein production could provide new avenues to improve the secretion and quality of protein therapeutics.

      PubDate: 2018-02-05T10:32:07Z
      DOI: 10.1016/j.copbio.2018.01.007
      Issue No: Vol. 53 (2018)
       
  • Continuous directed evolution for strain and protein engineering
    • Authors: Simon d’Oelsnitz; Andrew Ellington
      Pages: 158 - 163
      Abstract: Publication date: October 2018
      Source:Current Opinion in Biotechnology, Volume 53
      Author(s): Simon d’Oelsnitz, Andrew Ellington
      Continuous directed evolution is the ‘while loop’ of synthetic biology, autonomous cycles of mutation, selection, and self-replication that can lead to the rapid development of industrially relevant organisms, pathways, or molecules. Although this engineering strategy requires particular mutagenesis methods and well-defined selections, recent advances have facilitated its implementation. Control over selection pressure has been augmented by novel cost-effective continuous culturing devices with open source designs. New in vivo targeted mutagenesis methods have enabled continuous directed protein evolution in various organisms. Furthermore, advances in automation have enabled rational, semi-continuous directed evolution strategies that may yield fewer artefacts or parasites. Overall, continuous directed evolution is persistently demonstrating its capacity to rapidly generate biotechnologically valuable strains and proteins.
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      PubDate: 2018-02-15T10:39:38Z
      DOI: 10.1016/j.copbio.2017.12.020
      Issue No: Vol. 53 (2018)
       
  • A guide to manufacturing CAR T cell therapies
    • Authors: Philipp Vormittag; Rebecca Gunn; Sara Ghorashian; Farlan S Veraitch
      Pages: 164 - 181
      Abstract: Publication date: October 2018
      Source:Current Opinion in Biotechnology, Volume 53
      Author(s): Philipp Vormittag, Rebecca Gunn, Sara Ghorashian, Farlan S Veraitch
      In recent years, chimeric antigen receptor (CAR) modified T cells have been used as a treatment for haematological malignancies in several phase I and II trials and with Kymriah of Novartis and Yescarta of KITE Pharma, the first CAR T cell therapy products have been approved. Promising clinical outcomes have yet been tempered by the fact that many therapies may be prohibitively expensive to manufacture. The process is not yet defined, far from being standardised and often requires extensive manual handling steps. For academia, big pharma and contract manufacturers it is difficult to obtain an overview over the process strategies and their respective advantages and disadvantages. This review details current production processes being used for CAR T cells with a particular focus on efficacy, reproducibility, manufacturing costs and release testing. By undertaking a systematic analysis of the manufacture of CAR T cells from reported clinical trial data to date, we have been able to quantify recent trends and track the uptake of new process technology. Delivering new processing options will be key to the success of the CAR-T cells ensuring that excessive manufacturing costs do not disrupt the delivery of exciting new therapies to the wide possible patient cohort.
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      PubDate: 2018-02-25T19:18:08Z
      DOI: 10.1016/j.copbio.2018.01.025
      Issue No: Vol. 53 (2018)
       
  • Understanding biopharmaceutical production at single nucleotide resolution
           using ribosome footprint profiling
    • Authors: Ioanna Tzani; Craig Monger; Paul Kelly; Niall Barron; Ronan M Kelly; Colin Clarke
      Pages: 182 - 190
      Abstract: Publication date: October 2018
      Source:Current Opinion in Biotechnology, Volume 53
      Author(s): Ioanna Tzani, Craig Monger, Paul Kelly, Niall Barron, Ronan M Kelly, Colin Clarke
      Biopharmaceuticals such as monoclonal antibodies have revolutionised the treatment of a variety of diseases. The production of recombinant therapeutic proteins, however, remains expensive due to the manufacturing complexity of mammalian expression systems and the regulatory burden associated with administrating these medicines to patients in a safe and efficacious manner. In recent years, academic and industrial groups have begun to develop a greater understanding of the biology of host cell lines, such as Chinese hamster ovary (CHO) cells and utilise that information for process development and cell line engineering. In this review, we focus on ribosome footprint profiling (RiboSeq), an exciting next generation sequencing (NGS) method that provides genome-wide information on translation, and discuss how its application can transform our understanding of therapeutic protein production.

      PubDate: 2018-02-25T19:18:08Z
      DOI: 10.1016/j.copbio.2018.01.030
      Issue No: Vol. 53 (2018)
       
  • Genetic engineering of host organisms for pharmaceutical synthesis
    • Authors: Joseph H Collins; Eric M Young
      Pages: 191 - 200
      Abstract: Publication date: October 2018
      Source:Current Opinion in Biotechnology, Volume 53
      Author(s): Joseph H Collins, Eric M Young
      Pharmaceutical production hosts may be derived from almost any organism, from Chinese Hamster Ovary (CHO) cell lines to isolated actinomycetes. Each host can be improved, historically only through adaptive evolution. Recently, the maturation of organism engineering has expanded the available models, methods, and tools for altering host phenotypes. New tools like CRISPR-associated endonucleases promise to enable precise cellular reprogramming and to access previously intractable hosts. In this review, we discuss the most recent advances in engineering several types of pharmaceutical production hosts. These include model organisms, potential platform hosts with advantageous metabolism or physiology, specialized producers capable of unique biosynthesis, and CHO, the most widely used recombinant protein production host. To realize improved engineered hosts, an increasing number of approaches involving DNA sequencing and synthesis, host rewriting technologies, computational methods, and organism engineering strategies must be used. Integrative workflows that enable application of the right combination of methods to the right production host could enable economical production solutions for emerging human health treatments.

      PubDate: 2018-02-25T19:18:08Z
      DOI: 10.1016/j.copbio.2018.02.001
      Issue No: Vol. 53 (2018)
       
  • Emerging platforms for co-utilization of one-carbon substrates by
           photosynthetic organisms
    • Authors: Abhay K Singh; Ganesh M Kishore; Himadri B Pakrasi
      Pages: 201 - 208
      Abstract: Publication date: October 2018
      Source:Current Opinion in Biotechnology, Volume 53
      Author(s): Abhay K Singh, Ganesh M Kishore, Himadri B Pakrasi
      One-carbon substrates have generated increasing attention as long-term sustainable feedstocks for biobased production of fuels and chemicals. However, their physicochemical properties present significant biological and operational challenges for commercial bioprocesses including kinetically slower substrate activation, high energetic cost of assimilation, low mass transfer, substrate toxicity, and low productivity titers. Several different routes including optimization of native pathways, synthetic pathways, and hybrid methods are being explored to overcome these challenges. Integration of emerging biological solutions with process improvements is enabling faster bioprocess development for cost-effective conversion of one-carbon substrates into fuels and chemicals.
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      PubDate: 2018-03-06T13:54:55Z
      DOI: 10.1016/j.copbio.2018.02.002
      Issue No: Vol. 53 (2018)
       
  • Stimuli-responsive polymeric materials for separation of biomolecules
    • Authors: Sinuo Tan; Kei Saito; Milton TW Hearn
      Pages: 209 - 223
      Abstract: Publication date: October 2018
      Source:Current Opinion in Biotechnology, Volume 53
      Author(s): Sinuo Tan, Kei Saito, Milton TW Hearn
      Stimuli-responsive polymeric (SRP) materials undergo changes in their physical morphologies and chemical properties in response to small changes in their external environment, such as temperature, pH or light. When immobilised, SRP materials, fabricated in various formats and compositions, provide new opportunities for the separation of products generated by the biotechnology industry. This Current Opinion highlights the potential of these functional materials for the capture, purification and analysis of these products via batch capture methods, column chromatography or electrophoresis, drawing on break-through developments achieved particularly over the last five years.

      PubDate: 2018-03-19T07:01:26Z
      DOI: 10.1016/j.copbio.2018.02.011
      Issue No: Vol. 53 (2018)
       
  • Synthetic biology in probiotic lactic acid bacteria: At the frontier of
           living therapeutics
    • Authors: Zachary JS Mays; Nikhil U Nair
      Pages: 224 - 231
      Abstract: Publication date: October 2018
      Source:Current Opinion in Biotechnology, Volume 53
      Author(s): Zachary JS Mays, Nikhil U Nair
      The trillions of microbes hosted by humans can dictate health or illness depending on a multitude of genetic, environmental, and lifestyle factors that help define the human ecosystem. As the human microbiota is characterized, so can the interconnectivity of microbe–host-disease be realized and manipulated. Designing microbes as therapeutic agents can not only enable targeted drug delivery but also restore homeostasis within a perturbed microbial community. Used for centuries in fermentation and preservation of food, lactic acid bacteria (LAB) have a long history of safe, and occasionally health promoting, interactions with the human gut, making them ideal candidates for engineered functionality. This review outlines available genetic tools, recent developments in biomedical applications, as well as potential future applications of synthetic biology to program LAB-based therapeutic systems.
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      PubDate: 2018-03-19T07:01:26Z
      DOI: 10.1016/j.copbio.2018.01.028
      Issue No: Vol. 53 (2018)
       
  • Computational approaches in design of nucleic acid-based therapeutics
    • Authors: Mark Sherman; Lydia Contreras
      Pages: 232 - 239
      Abstract: Publication date: October 2018
      Source:Current Opinion in Biotechnology, Volume 53
      Author(s): Mark Sherman, Lydia Contreras
      Recent advances in computational and experimental methods have led to novel avenues for therapeutic development. Utilization of nucleic acids as therapeutic agents and/or targets has been recently gaining attention due to their potential as high-affinity, selective molecular building blocks for various therapies. Notably, development of computational algorithms for predicting accessible RNA binding sites, identifying therapeutic target sequences, modeling delivery into tissues, and designing binding aptamers have enhanced therapeutic potential for this new drug category. Here, we review trends in drug development within the pharmaceutical industry and ways by which nucleic acid-based drugs have arisen as effective therapeutic candidates. In particular, we focus on computational and experimental approaches to nucleic acid-based drug design, commenting on challenges and outlooks for future applications.
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      PubDate: 2018-03-19T07:01:26Z
      DOI: 10.1016/j.copbio.2017.12.001
      Issue No: Vol. 53 (2018)
       
  • In vivo systems biology approaches to chronic immune/inflammatory
           pathophysiology
    • Authors: Alina Starchenko; Douglas A Lauffenburger
      Pages: 9 - 16
      Abstract: Publication date: August 2018
      Source:Current Opinion in Biotechnology, Volume 52
      Author(s): Alina Starchenko, Douglas A Lauffenburger
      Systems biology offers an emphasis on integrative computational analysis of complex multi-component processes to enhance capability for predictive insights concerning operation of those processes. The immune system represents a prominent arena in which such processes are manifested for vital roles in physiology and pathology, encompassing dozens of cell types and hundreds of reciprocal interactions. Chronic, debilitating pathologies involving immune system dysregulation have become recognized as increasing in incidence over recent decades. While clinical consequences of immune dysregulation in such pathologies are well characterized, treatment options remain limited and focus on ameliorating symptoms. Because it is difficult to recapitulate more than a severely limited facet of the immune system in vitro, application of systems biology approaches to autoimmune and inflammatory pathophysiology in vivo has opened a new door toward discerning disease sub-groups and developing associated stratification strategies for patient treatment. In particular, early instances of these approaches have demonstrated advances in uncovering previously under-appreciated dysregulation of signaling networks between immune system and tissue cells, raising promise for improving upon current therapeutic approaches.
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      PubDate: 2018-03-06T13:54:55Z
      DOI: 10.1016/j.copbio.2018.02.006
      Issue No: Vol. 52 (2018)
       
  • Bridging intracellular scales by mechanistic computational models
    • Authors: Lukas Andreas Widmer; Jörg Stelling
      Pages: 17 - 24
      Abstract: Publication date: August 2018
      Source:Current Opinion in Biotechnology, Volume 52
      Author(s): Lukas Andreas Widmer, Jörg Stelling
      The impact of intracellular spatial organization beyond classical compartments on processes such as cell signaling is increasingly recognized. A quantitative, mechanistic understanding of cellular systems therefore needs to account for different scales in at least three coordinates: time, molecular abundances, and space. Mechanistic mathematical models may span all these scales, but corresponding multi-scale models need to resolve mechanistic details on small scales while maintaining computational tractability for larger ones. This typically results in models that combine different levels of description: from a microscopic representation of chemical reactions up to continuum dynamics in space and time. We highlight recent progress in bridging these model classes and outline current challenges in multi-scale models such as active transport and dynamic geometries.
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      PubDate: 2018-02-25T19:18:08Z
      DOI: 10.1016/j.copbio.2018.02.005
      Issue No: Vol. 52 (2018)
       
  • Synthesis of non-canonical branched-chain amino acids in Escherichia coli
           and approaches to avoid their incorporation into recombinant proteins
    • Abstract: Publication date: October 2018
      Source:Current Opinion in Biotechnology, Volume 53
      Author(s): Christian Reitz, Qin Fan, Peter Neubauer
      In E. coli the non-canonical amino acids acids norvaline, norleucine, and β-methylnorleucine, which derive from an off-pathway of the branched-chain amino acid synthesis route are synthesized and incorporated into cellular and recombinant proteins. The synthesis of these amino acids is supported by a high flux of glucose through the glycolytic pathway in combination with a derepression of the enzymes of the branched chain amino acid pathway, for example, when leucine-rich proteins are produced. Avoiding the synthesis and misincorporation of these amino acids has been challenging, especially in large-scale pharmaceutical processes where the problem is boosted by the typical fed-batch production and the technical limitation of mass transfer in the bioreactors. Despite its industrial importance, so far this issue has not been discussed comprehensively. Therefore this paper reviews, firstly, the specific pathway of the non-canonical branched chain amino acids starting at pyruvate, secondly, the molecular factors for their misincorporation, and thirdly, approaches to avoid this misincoporation. While the synthesis of these amino acids is difficult to prevent due to the broad promiscuity of the connected enzymes, recent studies on the control mechanisms of aminoacyl tRNA synthetases open new opportunities to avoid this misincorporation.

      PubDate: 2018-06-05T22:28:00Z
       
  • How scalable and suitable are single-use bioreactors'
    • Abstract: Publication date: October 2018
      Source:Current Opinion in Biotechnology, Volume 53
      Author(s): Stefan Junne, Peter Neubauer
      Although the scalability of stainless steel bioreactors has been investigated for more than 50 years, and many methods for the characterization of these bioreactors have been evolved, the investigation of scalability of single-use bioreactors (SUBs) contains several new challenges. SUBs permit a versatile design that is not necessarily oriented towards classical geometric conditions and allows a wide variety of mixing principles. Among the various principles might be some advantageous for the cultivation of particular types of shear-sensitive cells, such as mycelium-forming organisms and stem cells. In addition, these systems must be applicable in emerging fields like continuous perfusion processes. In this paper, we will discuss the current state of disposable bioreactors in terms of cultivation performances, with a special emphasis on the impact of physiological properties of cells across several scales and cultivation modes beyond classical engineering parameters.
      Graphical abstract image

      PubDate: 2018-05-28T08:10:59Z
       
 
 
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