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1.
  • Noodleman, L., et al. (author)
  • Insights into properties and energetics of iron-sulfur proteins from simple clusters to nitrogenase
  • 2002
  • In: Current opinion in chemical biology. - 1367-5931 .- 1879-0402. ; 6:2, s. 259-273
  • Research review (peer-reviewed)abstract
    • Some of the principal physical features of iron-sulfur clusters in proteins are analyzed, including metal-ligand covalency, spin polarization, spin coupling, valence delocalization, valence interchange and small reorganization energies, with emphasis on recent spectroscopic and theoretical work. The current state of structural, spectroscopic, and computational knowledge for the iron-sulfur clusters in the nitrogenase iron and iron-molybdenum proteins is examined by comparison and contrast to 'simpler' iron-sulfur clusters. The differing interactions of the nitrogenase iron and iron-molybdenum clusters compared with those of other iron-sulfur clusters with the protein and solvent environment are also explored.
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2.
  • Blom, Hans, et al. (author)
  • STED microscopy : towards broadened use and scope of applications
  • 2014
  • In: Current opinion in chemical biology. - : Elsevier. - 1367-5931 .- 1879-0402. ; 20:1, s. 127-133
  • Research review (peer-reviewed)abstract
    • High resolution Stimulated Emission Depletion (STED) microscopy has been demonstrated for fundamental studies in cells, living tissue and organisms. Today, a major trend in the STED technique development is to make the instruments simpler and more user-friendly, without compromising performance. This has become possible by new low-cost, turn-key laser technology and by implementing specifically designed phase plates and polarization elements, extending and simplifying the shaping of the laser beam profiles. These simpler and cheaper realizations of STED are now becoming more broadly available. In parallel with the continuous development of sample preparation and fluorophore reporter molecules ultimately setting the limit of the image quality, contrast and resolution, we can thus expect a significant increase in the use of STED, in science as well as for clinical and drug development purposes.
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3.
  • Buijs, Nicolaas, 1985, et al. (author)
  • Advanced biofuel production by the yeast Saccharomyces cerevisiae
  • 2013
  • In: Current Opinion in Chemical Biology. - : Elsevier BV. - 1879-0402 .- 1367-5931. ; 17:3, s. 480-488
  • Research review (peer-reviewed)abstract
    • Replacement of conventional transportation fuels with biofuels will require production of compounds that can cover the complete fuel spectrum, ranging from gasoline to kerosene. Advanced biofuels are expected to play an important role in replacing fossil fuels because they have improved properties compared with ethanol and some of these may have the energy density required for use in heavy duty vehicles, ships, and aviation. Moreover, advanced biofuels can be used as drop-in fuels in existing internal combustion engines. The yeast cell factory Saccharomyces cerevisiae can be turned into a producer of higher alcohols (1-butanol and isobutanol), sesquiterpenes (farnesene and bisabolene), and fatty acid ethyl esters (biodiesel), and here we discusses progress in metabolic engineering of S. cerevisiae for production of these advanced biofuels.
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4.
  • Cheon, Seungwoo, et al. (author)
  • Recent trends in metabolic engineering of microorganisms for the production of advanced biofuels
  • 2016
  • In: Current opinion in chemical biology. - : Elsevier. - 1367-5931 .- 1879-0402. ; 35, s. 10-21
  • Journal article (peer-reviewed)abstract
    • As climate change has become one of the major global risks, our heavy dependence on petroleum-derived fuels has received much public attention. To solve such problems, production of sustainable fuels has been intensively studied over the past years. Thanks to recent advances in synthetic biology and metabolic engineering technologies, bio-based platforms for advanced biofuels production have been developed using various microorganisms. The strategies for production of advanced biofuels have converged upon four major metabolic routes: the 2-ketoacid pathway, the fatty acid synthesis (FAS) pathway, the isoprenoid pathway, and the reverse β-oxidation pathway. Additionally, the polyketide synthesis pathway has recently been attracting interest as a promising alternative biofuel production route. In this article, recent trends in advanced biofuels production are reviewed by categorizing them into three types of advanced biofuels: alcohols, biodiesel and jet fuel, and gasoline. Focus is given on the strategies of employing synthetic biology and metabolic engineering for the development of microbial strains producing advanced fuels. Finally, the prospects for future advances needed to achieve much more efficient bio-based production of advanced biofuels are discussed, focusing on designing advanced biofuel production pathways coupled with screening, modifying, and creating novel enzymes.
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5.
  • Fink, Michael J., et al. (author)
  • Redesign of water networks for efficient biocatalysis
  • 2017
  • In: Current opinion in chemical biology. - : ELSEVIER SCI LTD. - 1367-5931 .- 1879-0402. ; 37, s. 107-114
  • Research review (peer-reviewed)abstract
    • Herein we highlight recent findings on the importance of water networks in proteins, and their redesign and reconfiguration as a new engineering strategy to generate enzymes with modulated binding affinity and improved catalytic versatility. Traditionally, enzyme engineering and drug design have focused on tailoring direct and favorable interactions between protein surfaces and ligands/transition states to achieve stronger binding, or an accelerated manufacturing of medicines, biofuels, fine chemicals and materials. In contrast, the opportunity to relocate water molecules in solvated binding pockets by protein design to improve overall energetics remains essentially unexplored, and fundamental understanding of the elusive processes involved is poor. Rewiring water networks in protein interiors impacts binding affinity, catalysis and the thermodynamic signature of biochemical processes through dynamic mechanisms, and thus has great potential to enhance binding specificity, accelerate catalysis and provide new reaction mechanisms and chemistry, that were not yet explored in nature.
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6.
  • Fletcher, John, 1978, et al. (author)
  • Label free biochemical 2D and 3D imaging using secondary ion mass spectrometry.
  • 2011
  • In: Current opinion in chemical biology. - : Elsevier BV. - 1879-0402 .- 1367-5931. ; 15:5, s. 733-40
  • Research review (peer-reviewed)abstract
    • Time-of-flight secondary ion mass spectrometry (ToF-SIMS) provides a method for the detection of native and exogenous compounds in biological samples on a cellular scale. Through the development of novel ion beams the amount of molecular signal available from the sample surface has been increased. Through the introduction of polyatomic ion beams, particularly C(60), ToF-SIMS can now be used to monitor molecular signals as a function of depth as the sample is eroded thus proving the ability to generate 3D molecular images. Here we describe how this new capability has led to the development of novel instrumentation for 3D molecular imaging while also highlighting the importance of sample preparation and discuss the challenges that still need to be overcome to maximise the impact of the technique.
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7.
  • Gabelica, Valérie, et al. (author)
  • Fundamentals of ion mobility spectrometry
  • 2018
  • In: Current opinion in chemical biology. - : Elsevier BV. - 1367-5931 .- 1879-0402. ; 42, s. 51-59
  • Research review (peer-reviewed)abstract
    • Fundamental questions in ion mobility spectrometry have practical implications for analytical applications in general, and omics in particular, in three respects. (1) Understanding how ion mobility and collision cross section values depend on the collision gas, on the electric field and on temperature is crucial to ascertain their transferability across instrumental platforms. (2) Predicting collision cross section values for new analytes is necessary to exploit the full potential of ion mobility in discovery workflows. (3) Finally, understanding the fate of ion structures in the gas phase is essential to infer meaningful information on solution structures based on gas-phase ion mobility measurements. We review here the most recent advances in ion mobility fundamentals, relevant to these three aspects.
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8.
  • Hammer, Stephan C., et al. (author)
  • Squalene hopene cyclases : highly promiscuous and evolvable catalysts for stereoselective CC and CX bond formation
  • 2013
  • In: Current opinion in chemical biology. - : Elsevier. - 1367-5931 .- 1879-0402. ; 17:2, s. 293-300
  • Journal article (peer-reviewed)abstract
    • A review. We review here how the inherent promiscuous nature, as well as the evolvability of terpene cyclase enzymes enables new applications in chem. We mainly focus on squalene hopene cyclases, class II triterpene synthases that use a proton-initiated cationic polycyclization cascade to form carbopolycyclic products. We highlight recent findings to demonstrate that these enzymes are capable of activating different functionalities other than the traditional terminal isoprene CC-group as well as being compatible with a wide range of nucleophiles beyond the 'ene-functionality'. Thus, squalene hopene cyclases demonstrate a great potential to be used as a toolbox for general Bronsted acid catalysis.
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9.
  • Jain, Mahendra Kumar, et al. (author)
  • Coupling of the i-face and the active site of phospholipase A2 for interfacial activation.
  • 2006
  • In: Current opinion in chemical biology. - : Elsevier BV. - 1367-5931 .- 1879-0402. ; 10:5, s. 473-479
  • Journal article (peer-reviewed)abstract
    • Interfacial enzymes bind to organized interfaces where they access their substrates. As an example of interfacial activation, phospholipase A2 has an observed rate of hydrolysis of the sn-2-acyl chain of phospholipids at bilayer and micellar interfaces that is more than 1,000 times larger than with monodisperse phospholipids. The major challenge for the study of interfacial enzymes is to correlate the elementary steps of the interfacial function of the enzyme with the structure of the enzyme at the interface. Having kinetically resolved the steps of the interfacial turnover cycle, here we outline our recent (mostly since 2000) approaches to address remaining issues of interfacial activation and also the protocols that are likely to provide insights into the distinguishing structural features of the interface-activated enzyme.
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10.
  • Kohls, Hannes, et al. (author)
  • Recent achievements in developing the biocatalytic toolbox for chiral amine synthesis
  • 2014
  • In: Current opinion in chemical biology. - : Elsevier BV. - 1367-5931 .- 1879-0402. ; 19, s. 180-192
  • Journal article (peer-reviewed)abstract
    • Novel enzyme activities and chemoenzymatic reaction concepts have considerably expanded the biocatalytic toolbox for chiral amine synthesis. Creating new activities or extending the scope of existing enzymes by protein engineering is a common trend in biocatalysis and in chiral amine synthesis specifically. For instance, an amine dehydrogenase that allows for the direct asymmetric amination of ketones with ammonia was created by mutagenesis of an L-amino acid dehydrogenase. Another trend in chiral amine chemistry is the development of strategies allowing for the synthesis of secondary amines. For example the smart choice of substrates for amine transaminases provided access to secondary amines by chemoenzymatic reactions. Furthermore novel biocatalysts for the synthesis of secondary amines such as imine reductases and Pictet-Spenglerases have been identified and applied. Recent examples showed that the biocatalytic amine synthesis is emerging from simple model reactions towards industrial scale preparation of pharmaceutical relevant substances, for instance, as shown in the synthesis of a Janus kinase 2 inhibitor using an amine transaminase. A comparison of important process parameters such as turnover number and space-time yield demonstrates that biocatalytic strategies for asymmetric reductive amination are maturing and can already compete with established chemical methods.
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11.
  • Kortesniemi, Maaria, et al. (author)
  • Nutritional metabolomics: Recent developments and future needs
  • 2023
  • In: Current Opinion in Chemical Biology. - 1879-0402 .- 1367-5931. ; 77
  • Research review (peer-reviewed)abstract
    • Metabolomics has rapidly been adopted as one of the key methods in nutrition research. This review focuses on the recent developments and updates in the field, including the analytical methodologies that encompass improved instrument sensitivity, sampling techniques and data integration (multiomics). Metabolomics has advanced the discovery and validation of dietary biomarkers and their implementation in health research. Metabolomics has come to play an important role in the understanding of the role of small molecules resulting from the diet–microbiota interactions when gut microbiota research has shifted towards improving the understanding of the activity and functionality of gut microbiota rather than composition alone. Currently, metabolomics plays an emerging role in precision nutrition and the recent developments therein are discussed.
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12.
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13.
  • Mahecic, Dora, et al. (author)
  • Strategies for increasing the throughput of super-resolution microscopies
  • 2019
  • In: Current opinion in chemical biology. - : ELSEVIER SCI LTD. - 1367-5931 .- 1879-0402. ; 51, s. 84-91
  • Research review (peer-reviewed)abstract
    • Fluorescence microscopy methods have been developed to circumvent the diffraction limit by exploiting nonlinearities in the interactions between light and fluorophores. Initially, these methods were up to orders of magnitude slower than standard microscopies. In recent years, a wide array of technological advances have increased the throughput of super-resolution microscopies, through parallelization, smart scanning or data processing, and sample expansion. Here, we review re cent innovations for increased throughput, some applications that have benefitted from them, and how they could be improved in the future.
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14.
  • Meehan, Richard R., et al. (author)
  • DNA methylation as a genomic marker of exposure to chemical and environmental agents
  • 2018
  • In: Current opinion in chemical biology. - : ELSEVIER SCI LTD. - 1367-5931 .- 1879-0402. ; 45, s. 48-56
  • Research review (peer-reviewed)abstract
    • Recent progress in interpreting comprehensive genetic and epigenetic profiles for human cellular states has contributed new insights into the developmental origins of disease, elucidated novel signalling pathways and enhanced drug discovery programs. A similar comprehensive approach to decoding the epigenetic readouts from chemical challenges in vivo would yield new paradigms for monitoring and assessing environmental exposure in model systems and humans.
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15.
  • Miao, Rui, et al. (author)
  • Current processes and future challenges of photoautotrophic production of acetyl-CoA-derived solar fuels and chemicals in cyanobacteria
  • 2020
  • In: Current opinion in chemical biology. - : Elsevier BV. - 1367-5931 .- 1879-0402. ; 59, s. 69-76
  • Research review (peer-reviewed)abstract
    • The production of fuels and other valuable chemicals via biological routes has gained significant attention during last decades. Cyanobacteria are prokaryotes that convert solar energy to chemical compounds in vivo in direct processes. Intensive studies have been carried out with the aim of engineering cyanobacteria as microfactories for solar fuel and chemical production. Engineered strains of photosynthetic cyanobacteria can produce different compounds on a proof-ofconcept level, but few products show titers comparable with those achieved in heterotrophic organisms. Efficient genetic engineering tools and metabolic modeling can accelerate the development of solar fuel and chemical production in cyanobacteria. This review addresses the most recent approaches to produce solar fuels and chemicals in engineered cyanobacteria with a focus on acetyl-CoA-dependent products.
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18.
  • Salihovic, Samira, Associate Senior Lecturer, 1985-, et al. (author)
  • Recent advances towards mass spectrometry-based clinical lipidomics
  • 2023
  • In: Current opinion in chemical biology. - : Current Opinion. - 1367-5931 .- 1879-0402. ; 76
  • Research review (peer-reviewed)abstract
    • The objective of this review is to provide a comprehensive summary of the latest methodological advancements and emerging patterns in utilizing lipidomics in clinical research.In this review, we assess the recent advancements in lipidomics methodologies that exhibit high levels of selectivity and sensitivity, capable of generating numerous molecular lipid species from limited quantities of biological matrices. The reviewed studies demonstrate that molecular lipid signatures offer new opportunities for precision medicine by providing sensitive diagnostic tools for disease prediction and monitoring. Moreover, the latest innovations in microsampling techniques have the potential to make a substantial contribution to clinical lipidomics. The review also shows that more work is needed to harmonize results across diverse lipidomics platforms and avoid significant errors in analysis and reporting. The increased implementation of internal standards and standard reference materials in analytical workflows will aid in this direction.
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19.
  • Wang, Jinfan, et al. (author)
  • Ribosomal incorporation of unnatural amino acids : lessons and improvements from fast kinetics studies
  • 2018
  • In: Current opinion in chemical biology. - : Elsevier. - 1367-5931 .- 1879-0402. ; 46, s. 180-187
  • Research review (peer-reviewed)abstract
    • Technologies for genetically programming ribosomal incorporation of unnatural amino acids are expanding and have created many exciting applications. However, these applications are generally limited by low efficiencies of the unnatural incorporations. Here we review our current mechanistic understanding of these limitations delineated from in vitro fast kinetics. Rate limitation occurs by different mechanisms, depending on the classes of the unnatural amino acids and the tRNA adaptors. This new understanding has led to several ways of improving the incorporation efficiencies, as well as challenges of dogma on rate-limiting steps in protein synthesis in natural cells.
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20.
  • Widersten, Mikael (author)
  • Protein engineering for development of new hydrolytic biocatalysts
  • 2014
  • In: Current opinion in chemical biology. - : Elsevier BV. - 1367-5931 .- 1879-0402. ; 21, s. 42-47
  • Research review (peer-reviewed)abstract
    • Hydrolytic enzymes play important roles as biocatalysts in chemical synthesis. The chemical versatility and structurally sturdy features of Candida antarctica lipase B has placed this enzyme as a common utensil in the synthetic tool-box. In addition to catalyzing acyl transfer reactions, a number of promiscuous activities have been described recently. Some of these new enzyme activities have been amplified by mutagenesis. Epoxide hydrolases are of interest due to their potential as catalysts in asymmetric synthesis. This current update discusses recent development in the engineering of lipases and epoxide hydrolases aiming to generate new biocatalysts with refined features as compared to the wild-type enzymes. Reported progress in improvements in reaction atom economy from dynamic kinetic resolution or enantioconvergence are also included.
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21.
  • Yung, PYK, et al. (author)
  • Evolution of epigenetic chromatin states
  • 2017
  • In: Current opinion in chemical biology. - : Elsevier BV. - 1879-0402 .- 1367-5931. ; 41, s. 36-42
  • Journal article (peer-reviewed)
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24.
  • Terenius, L (author)
  • Rational treatment of addiction
  • 1998
  • In: Current opinion in chemical biology. - : Elsevier BV. - 1367-5931. ; 2:4, s. 541-547
  • Journal article (peer-reviewed)
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27.
  • Poongavanam, Vasanthanathan, et al. (author)
  • Opportunities and guidelines for discovery of orally absorbed drugs in beyond rule of 5 space
  • 2018
  • In: Current Opinion in Chemical Biology. - : Elsevier BV. - 1367-5931. ; 44, s. 23-29
  • Research review (peer-reviewed)abstract
    • Recent years have seen a dramatic increase in the number of drugs approved in chemical space outside of Lipinski’s rule of 5, that is in what has been termed beyond rule of 5 (bRo5) space. The development of three major classes of oral drugs that treat HIV and HCV infections and the growing evidence that novel, difficult targets can be accessed has prompted research into understanding design of drugs displaying cell permeability, solubility and ultimately oral bioavailability in bRo5 space. Studies have found a consistent outer property limit for a reasonable chance of de novo designing oral bioavailability. In addition, several property-based guidelines, along with incorporation of chameleonic features, have emerged as strategies to aid design in bRo5 space. A more detailed understanding of the complex and environment dependent conformational landscape will likely be the focus of the next generation of guidelines allowing property predictions of ever more complex compounds. By pushing the boundaries of current orally designable chemical space we hope that discoveries will be made for fundamental science and also for discovery of novel therapeutics.
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28.
  • Ryde, Ulf (author)
  • Combined quantum and molecular mechanics calculations on metalloproteins.
  • 2003
  • In: Current Opinion in Chemical Biology. - 1879-0402. ; 7:1, s. 136-142
  • Research review (peer-reviewed)abstract
    • The combination of quantum mechanics and molecular mechanics (QM/MM) methods is one of the most promising approaches to study the structure, function and properties of proteins. The number of QM/MM applications on metalloproteins is steadily increasing, especially studies with density functional methods on redox-active metal centres. Recent developments include new parameterised methods to treat covalent bonds between the quantum and classical systems, methods to obtain free energy from QM/MM results, and the combination of quantum chemistry and protein crystallography.
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29.
  • van Zijl, Peter C. M., et al. (author)
  • Hyperpolarized MRI, functional MRI, MR spectroscopy and CEST to provide metabolic information in vivo
  • 2021
  • In: Current Opinion in Chemical Biology. - : Elsevier BV. - 1367-5931. ; 63, s. 209-218
  • Journal article (peer-reviewed)abstract
    • Access to metabolic information in vivo using magnetic resonance (MR) technologies has generally been the niche of MR spectroscopy (MRS) and spectroscopic imaging (MRSI). Metabolic fluxes can be studied using the infusion of substrates labeled with magnetic isotopes, with the use of hyperpolarization especially powerful. Unfortunately, these promising methods are not yet accepted clinically, where fast, simple, and reliable measurement and diagnosis are key. Recent advances in functional MRI and chemical exchange saturation transfer (CEST) MRI allow the use of water imaging to study oxygen metabolism and tissue metabolite levels. These, together with the use of novel data analysis approaches such as machine learning for all of these metabolic MR approaches, are increasing the likelihood of their clinical translation.
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