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Current Opinion in Biotechnology

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...
February 17, 2018: Current Opinion in Biotechnology
Shelesh Agrawal, Dries Seuntjens, Pieter De Cocker, Susanne Lackner, Siegfried E Vlaeminck
Twenty years ago, mainstream partial nitritation/anammox (PN/A) was conceptually proposed as pivotal for a more sustainable treatment of municipal wastewater. Its economic potential spurred research, yet practice awaits a comprehensive recipe for microbial resource management. Implementing mainstream PN/A requires transferable and operable ways to steer microbial competition as to meet discharge requirements on a year-round basis at satisfactory conversion rates. In essence, the competition for nitrogen, organic carbon and oxygen is grouped into 'ON/OFF' (suppression/promotion) and 'IN/OUT' (wash-out/retention and seeding) strategies, selecting for desirable conversions and microbes...
February 16, 2018: Current Opinion in Biotechnology
Catarina Loureiro, Marnix H Medema, John van der Oost, Detmer Sipkema
Microorganisms are Nature's little engineers of a remarkable array of bioactive small molecules that represent most of our new drugs. The wealth of genomic and metagenomic sequence data generated in the last decade has shown that the majority of novel biosynthetic gene clusters (BGCs) is identified from cultivation-independent studies, which has led to a strong expansion of the number of microbial taxa known to harbour BGCs. The large size and repeat sequences of BGCs remain a bioinformatic challenge, but newly developed software tools have been created to overcome these issues and are paramount to identify and select the most promising BGCs for further research and exploitation...
February 14, 2018: Current Opinion in Biotechnology
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...
February 13, 2018: Current Opinion in Biotechnology
Nico Joannes Claassens, Irene Sánchez-Andrea, Diana Zita Sousa, Arren Bar-Even
The replacement of fossil and agricultural feedstocks with sustainable alternatives for the production of chemicals and fuels is a societal and environmental necessity. This challenge can be tackled by using inorganic or one-carbon compounds as electron donors for microbial CO 2 fixation and bioproduction. Yet, considering the wide array of microbial electron donors, which are the best suited for bioindustry? Here, we propose criteria to evaluate these compounds, considering factors such as production methods, physicochemical properties, and microbial utilization...
February 13, 2018: Current Opinion in Biotechnology
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...
February 13, 2018: Current Opinion in Biotechnology
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...
February 13, 2018: Current Opinion in Biotechnology
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...
February 12, 2018: Current Opinion in Biotechnology
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...
February 11, 2018: Current Opinion in Biotechnology
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...
February 9, 2018: Current Opinion in Biotechnology
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...
February 6, 2018: Current Opinion in Biotechnology
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...
February 3, 2018: Current Opinion in Biotechnology
Ludmila Chistoserdova
This review summarizes developments in the field of applied research involving microbial conversion of single carbon compounds (methane, methanol, CO2). The potential of the microorganisms involved in biotechnological applications could be realized via engineering native C1 utilizers toward higher output of value-added compounds, including biofuels, or via production of value chemicals as parts of novel, heterologously expressed biochemical pathways. Alternatively, C1 metabolism could be implemented in traditional industrial platforms (Escherichia coli, yeast), via introduction of specific metabolic modules...
February 3, 2018: Current Opinion in Biotechnology
Kengo Sasaki, Daisuke Sasaki, Kazuhide Kamiya, Shuji Nakanishi, Akihiko Kondo, Souichiro Kato
Microbial electrochemical systems (MESs) are expected to be put into practical use as an environmental technology that can support a future environmentally friendly society. However, conventional MESs present a challenge of inevitably increasing initial investment, mainly due to requirements for a large numbers of electrode assemblies. In this review, we introduce electrochemical biotechnologies that are under development and can minimize the required electrode assemblies. The novel biotechnologies, called electro-fermentation and indirect electro-stimulation, can drive specific microbial metabolism by electrochemically controlling intercellular and extracellular redox states, respectively...
February 3, 2018: Current Opinion in Biotechnology
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...
February 3, 2018: Current Opinion in Biotechnology
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)...
February 2, 2018: Current Opinion in Biotechnology
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...
February 2, 2018: Current Opinion in Biotechnology
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...
February 1, 2018: Current Opinion in Biotechnology
Ioannis Mougiakos, Elleke F Bosma, Joyshree Ganguly, John van der Oost, Richard van Kranenburg
High engineering efficiencies are required for industrial strain development. Due to its user-friendliness and its stringency, CRISPR-Cas-based technologies have strongly increased genome engineering efficiencies in bacteria. This has enabled more rapid metabolic engineering of both the model host Escherichia coli and non-model organisms like Clostridia, Bacilli, Streptomycetes and cyanobacteria, opening new possibilities to use these organisms as improved cell factories. The discovery of novel Cas9-like systems from diverse microbial environments will extend the repertoire of applications and broaden the range of organisms in which it can be used to create novel production hosts...
February 1, 2018: Current Opinion in Biotechnology
Christopher M Humphreys, Nigel P Minton
The future sustainable production of chemicals and fuels from non-petrochemical sources, while at the same time reducing greenhouse gas (GHG) emissions, represent two of society's greatest challenges. Microbial chassis able to grow on waste carbon monoxide (CO) and carbon dioxide (CO2) can provide solutions to both. Ranging from the anaerobic acetogens, through the aerobic chemoautotrophs to the photoautotrophic cyanobacteria, they are able to convert C1 gases into a range of chemicals and fuels which may be enhanced and extended through appropriate metabolic engineering...
January 31, 2018: Current Opinion in Biotechnology
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