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Current Opinion in Biotechnology

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https://www.readbyqxmd.com/read/29870877/synthesis-of-non-canonical-branched-chain-amino-acids-in-escherichia-coli-and-approaches-to-avoid-their-incorporation-into-recombinant-proteins
#1
REVIEW
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...
June 2, 2018: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/29753977/how-scalable-and-suitable-are-single-use-bioreactors
#2
REVIEW
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...
May 10, 2018: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/29729544/computational-protein-design-the-next-generation-tool-to-expand-synthetic-biology-applications
#3
REVIEW
Pablo Gainza-Cirauqui, Bruno Emanuel Correia
One powerful approach to engineer synthetic biology pathways is the assembly of proteins sourced from one or more natural organisms. However, synthetic pathways often require custom functions or biophysical properties not displayed by natural proteins, limitations that could be overcome through modern protein engineering techniques. Structure-based computational protein design is a powerful tool to engineer new functional capabilities in proteins, and it is beginning to have a profound impact in synthetic biology...
May 2, 2018: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/29891032/editorial-overview-systems-biology-data-discovery-delivery
#4
EDITORIAL
Nathan D Price, Eran Segal
No abstract text is available yet for this article.
June 2018: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/29891031/editorial-overview-nanobiotechnology-baby-steps-and-giant-strides-towards-molecular-mastery
#5
EDITORIAL
Mark Howarth, Alfonso Jaramillo
No abstract text is available yet for this article.
June 2018: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/29453029/systems-biology-of-the-human-microbiome
#6
REVIEW
Beatriz Peñalver Bernabé, Lauren Cralle, Jack A Gilbert
Recent research has shown that the microbiome-a collection of microorganisms, including bacteria, fungi, and viruses, living on and in a host-are of extraordinary importance in human health, even from conception and development in the uterus. Therefore, to further our ability to diagnose disease, to predict treatment outcomes, and to identify novel therapeutics, it is essential to include microbiome and microbial metabolic biomarkers in Systems Biology investigations. In clinical studies or, more precisely, Systems Medicine approaches, we can use the diversity and individual characteristics of the personal microbiome to enhance our resolution for patient stratification...
June 2018: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/29427919/the-building-blocks-of-successful-translation-of-proteomics-to-the-clinic
#7
REVIEW
Paul Kearney, J Jay Boniface, Nathan D Price, Leroy Hood
Recently, the first two multiplexed tests using selective reaction monitoring (SRM-MS) mass spectrometry have entered clinical practice. Despite different areas of indication, risk stratification in lung cancer and preterm birth, they share multiple steps in their development strategies. Here we review these strategies and their implications for successful translation of biomarkers to clinical practice. We believe that the identification of blood protein panels for the identification of disease phenotypes is now a reproducible and standard (albeit complex) process...
June 2018: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/29414440/induction-of-broadly-neutralizing-antibodies-in-germinal-centre-simulations
#8
REVIEW
Philippe A Robert, Andrea Lj Marschall, Michael Meyer-Hermann
Vaccines against mutating pathogens such as influenza, HIV, or plasmodium are poorly protective towards new evolving strains. Rare individuals naturally mount broadly neutralizing antibodies covering most strains, but the requirements for their induction are unknown. The antibody response to vaccination has been recapitulated by in silico models that proposed two opposite schemes: A theory of 'frustration' where one epitope at a time leads to optimal antibody breadth through sequential immunizations, that was proven successful for HIV vaccination in primates...
June 2018: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/29414439/quantitative-omic-data-empowers-bottom-up-systems-biology
#9
REVIEW
James T Yurkovich, Bernhard O Palsson
The large-scale generation of '-omic' data holds the potential to increase and deepen our understanding of biological phenomena, but the ability to synthesize information and extract knowledge from these data sets still represents a significant challenge. Bottom-up systems biology overcomes this hurdle through the integration of disparate -omic data types, and absolutely quantified experimental measurements allow for direct integration into quantitative, mechanistic models. The human red blood cell has served as a starting point for the application of systems biology approaches and has been the focus of a recent burst of generated quantitative metabolomics and proteomics data...
June 2018: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/29316481/rapidly-moving-new-bacteria-to-model-organism-status
#10
REVIEW
Hualan Liu, Adam M Deutschbauer
The paradigm of large research communities collectively working on a small number of model bacteria such as Escherichia coli and Bacillus subtilis is changing. While these classic model bacteria will continue to be important for advanced systems biology and new technology development, we envision that increasingly small research teams will be deeply investigating their own favorite strains, for example as new hosts for metabolic engineering or as key members of a complex microbiome. Given the lack of a research community and the sheer number of possible bacteria to interrogate, the development and application of technologies to rapidly and inexpensively advance these unstudied strains to 'model-organism' status is imperative...
June 2018: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/29288931/leveraging-and-coping-with-uncertainty-in-the-response-of-individual-cells-to-therapy
#11
REVIEW
José Reyes, Galit Lahav
Non-genetic heterogeneity fluctuates over diverse timescales, ranging from hours to months. In specific cases, such variability can profoundly impact the response of cell populations to therapy, in both antibiotic treatments in bacteria and chemotherapy in cancer. It is thus critical to understand the way phenotypes fluctuate in cell populations and the molecular sources of phenotypic diversity. Technical and analytical breakthroughs in the study of single cells have leveraged cellular heterogeneity to gain phenomenological and mechanistic insights of the phenotypic transitions that occur within isogenic cell populations over time...
June 2018: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/29278837/advances-in-gap-filling-genome-scale-metabolic-models-and-model-driven-experiments-lead-to-novel-metabolic-discoveries
#12
REVIEW
Shu Pan, Jennifer L Reed
With rapid improvements in next-generation sequencing technologies, our knowledge about metabolism of many organisms is rapidly increasing. However, gaps in metabolic networks exist due to incomplete knowledge (e.g., missing reactions, unknown pathways, unannotated and misannotated genes, promiscuous enzymes, and underground metabolic pathways). In this review, we discuss recent advances in gap-filling algorithms based on genome-scale metabolic models and the importance of both high-throughput experiments and detailed biochemical characterization, which work in concert with in silico methods, to allow a more accurate and comprehensive understanding of metabolism...
June 2018: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/29275251/emerging-whole-cell-modeling-principles-and-methods
#13
REVIEW
Arthur P Goldberg, Balázs Szigeti, Yin Hoon Chew, John Ap Sekar, Yosef D Roth, Jonathan R Karr
Whole-cell computational models aim to predict cellular phenotypes from genotype by representing the entire genome, the structure and concentration of each molecular species, each molecular interaction, and the extracellular environment. Whole-cell models have great potential to transform bioscience, bioengineering, and medicine. However, numerous challenges remain to achieve whole-cell models. Nevertheless, researchers are beginning to leverage recent progress in measurement technology, bioinformatics, data sharing, rule-based modeling, and multi-algorithmic simulation to build the first whole-cell models...
June 2018: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/29258014/modeling-metabolism-of-the-human-gut-microbiome
#14
REVIEW
Stefanía Magnúsdóttir, Ines Thiele
The human gut microbiome plays an important part in human health. The complexity of the microbiome makes it difficult to determine the detailed metabolic functions and cross-talk occurs between the individual species. In silico systems biology studies of the microbiome can help to identify metabolite exchanges among gut microbes. Constraint-based reconstruction and analysis methods use biochemically accurate genome-scale metabolic networks of microorganisms to simulate metabolism between species in a given microbiome and help generate novel hypotheses on microbial interactions...
June 2018: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/29232619/engineering-of-protein-nanopores-for-sequencing-chemical-or-protein-sensing-and-disease-diagnosis
#15
REVIEW
Shaoying Wang, Zhengyi Zhao, Farzin Haque, Peixuan Guo
Biological systems contain highly-ordered structures performing diverse functions. The elegant structures of biomachines have inspired the development of nanopores as single molecule sensors. Over the years, the utility of nanopores for detecting a wide variety of analytes have rapidly emerged for sensing, sequencing and diagnostic applications. Several protein channels with diverse shapes and sizes, such as motor channels from bacteriophage Phi29, SPP1, T3, and T4, as well as α-hemolysin, MspA, aerolysin, FluA, OmpF/G, CsgG, ClyA, have been continually investigated and developed as nanopores...
June 2018: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/29223465/biomedical-applications-of-genome-scale-metabolic-network-reconstructions-of-human-pathogens
#16
REVIEW
Laura J Dunphy, Jason A Papin
The growing global threat of antibiotic resistant human pathogens has coincided with improved methods for developing and using genome-scale metabolic network reconstructions. Consequently, there has been an increase in the number of high-quality reconstructions of relevant human and zoonotic pathogens. Novel biomedical applications of pathogen reconstructions focus on three key aspects of pathogen behavior: the evolution of antibiotic resistance, virulence factor production, and host-pathogen interactions. New methods using these reconstructions aim to improve understanding of microbe pathogenicity and guide the development of new therapeutic strategies...
June 2018: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/29223005/the-emerging-role-of-systems-biology-for-engineering-protein-production-in-cho-cells
#17
REVIEW
Chih-Chung Kuo, Austin Wt Chiang, Isaac Shamie, Mojtaba Samoudi, Jahir M Gutierrez, Nathan E Lewis
To meet the ever-growing demand for effective, safe, and affordable protein therapeutics, decades of intense efforts have aimed to maximize the quantity and quality of recombinant proteins produced in CHO cells. Bioprocessing innovations and cell engineering efforts have improved product titer; however, uncharacterized cellular processes and gene regulatory mechanisms still hinder cell growth, specific productivity, and protein quality. Herein, we summarize recent advances in systems biology and data-driven approaches aiming to unravel how molecular pathways, cellular processes, and extrinsic factors (e...
June 2018: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/29223004/towards-utilization-of-the-human-genome-and-microbiome-for-personalized-nutrition
#18
REVIEW
Stavros Bashiardes, Anastasia Godneva, Eran Elinav, Eran Segal
Generalized dietary and lifestyle guidelines have been formulated and published for decades now from a variety of relevant agencies in an attempt to guide people towards healthy choices. As the pandemic rise in metabolic diseases continues to increase, it has become clear that the one-fit-for-all diet approach does not work and that there is a significant variation in inter-individual responses to diet and lifestyle interventions. Recent technological advances have given an unprecedented insight into the sources of this variation, pointing towards our genome and microbiome as potentially and previously under-explored culprits contributing to individually unique dietary responses...
June 2018: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/29183001/tailoring-the-appearance-what-will-synthetic-cells-look-like
#19
REVIEW
Willem Kasper Spoelstra, Siddharth Deshpande, Cees Dekker
Recently, the bottom-up assembly of a synthetic cell has emerged as a daring novel approach that can be expected to have major impact in generating fundamental insight in the organization and function of actual biological cells, as well as in stimulating a broad range of applications from drug delivery systems to chemical nanofactories. A crucial feature of any such synthetic cell is the architectural scaffold that defines its identity, compartmentalizes its inner content, and serves as a protective and selective barrier against its environment...
June 2018: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/29179022/re-engineering-of-protein-motors-to-understand-mechanisms-biasing-random-motion-and-generating-collective-dynamics
#20
REVIEW
Ken'ya Furuta, Akane Furuta
A considerable amount of insight into the mechanisms of protein-based biomolecular motors has been accumulated over decades of research. However, our knowledge about the design principles of these motors is still limited. Even less is known about the design of multi-motor systems that perform various functions within the cell. Here we focus on constructive (or synthetic) approaches to biomolecular motors that could make a breakthrough in our understanding. Recent achievements include studies at different hierarchical levels of complexity: re-engineering of individual motors, construction of multi-motor systems, and generation of large-scale complex behaviour...
June 2018: Current Opinion in Biotechnology
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