Reply to Letter to the Editor.
PMID: 29452736 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - February 13, 2018 Category: Biochemistry Authors: Lam KS Tags: Curr Opin Chem Biol Source Type: research

Epigenetic chromatin modification by amber suppression technology.
Abstract The genetic incorporation of unnatural amino acids (UAAs) into proteins by amber suppression technology provides unique avenues to study protein structure, function and interactions both in vitro and in living cells and organisms. This approach has been particularly useful for studying mechanisms of epigenetic chromatin regulation, since these extensively involve dynamic changes in structure, complex formation and posttranslational modifications that are difficult to access by traditional approaches. Here, we review recent achievements in this field, emphasizing UAAs that help to unravel protein-protein i...
Source: Current Opinion in Chemical Biology - February 13, 2018 Category: Biochemistry Authors: Neumann H, Neumann-Staubitz P, Witte A, Summerer D Tags: Curr Opin Chem Biol Source Type: research

Harnessing natural DNA modifying activities for editing of the genome and epigenome.
Abstract The introduction of site-specific DNA modifications to the genome or epigenome presents great opportunities for manipulating biological systems. Such changes are now possible through the combination of DNA-modifying enzymes with targeting modules, including dCas9, that can localize the enzymes to specific sites. In this review, we take a DNA modifying enzyme-centric view of recent advances. We highlight the variety of natural DNA-modifying enzymes-including DNA methyltransferases, oxygenases, deaminases, and glycosylases-that can be used for targeted editing and discuss how insights into the structure and...
Source: Current Opinion in Chemical Biology - February 13, 2018 Category: Biochemistry Authors: DeNizio JE, Schutsky EK, Berrios KN, Liu MY, Kohli RM Tags: Curr Opin Chem Biol Source Type: research

Unique insights to intrinsically disordered proteins provided by ion mobility mass spectrometry.
Abstract Entire functional proteins as well as large regions of proteins lack structural elements which are resolvable via crystallography or NMR. These intrinsically disordered proteins (IDPs) or regions (IDRs) are often involved in cell regulation processes, for example in signalling hubs and as a result aberrant behaviour can cause or be representative of disease. As a consequence there is a pressing need to develop alternative structural methods for IDPs and the interactions that they may form with other proteins and/or with potential inhibitors of binding. One such method is ion mobility mass spectrometry (IM...
Source: Current Opinion in Chemical Biology - February 8, 2018 Category: Biochemistry Authors: Stuchfield D, Barran P Tags: Curr Opin Chem Biol Source Type: research

Enzymatic amidation for industrial applications.
Abstract Nature has developed a robust toolbox for the formation of amide bonds, enabling a variety of disconnections applicable to small molecule synthesis. In spite of this, the exploitation of biocatalytic techniques for industrial synthesis remains limited to a few very important cases. This review discusses previously demonstrated techniques for the biocatalytic synthesis of amide bonds, reviews examples of industrial scale-up of these techniques, and identifies a number of limitations to the scalability within the current state of the art. PMID: 29414531 [PubMed - as supplied by publisher] (Source: Curr...
Source: Current Opinion in Chemical Biology - February 3, 2018 Category: Biochemistry Authors: Dorr BM, Fuerst DE Tags: Curr Opin Chem Biol Source Type: research

Halogenases: powerful tools for biocatalysis (mechanisms applications and scope).
PMID: 29414530 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - February 1, 2018 Category: Biochemistry Authors: Gkotsi DS, Dhaliwal J, McLachlan MM, Mulholand KR, Goss RJ Tags: Curr Opin Chem Biol Source Type: research

Understanding protein-drug interactions using ion mobility-mass spectrometry.
Abstract Ion mobility-mass spectrometry (IM-MS) is an important addition to the analytical toolbox for the structural evaluation of proteins, and is enhancing many areas of biophysical analysis. Disease-associated proteins, including enzymes such as protein kinases, transcription factors exemplified by p53, and intrinsically disordered proteins, including those prone to aggregation, are all amenable to structural analysis by IM-MS. In this review we discuss how this powerful technique can be used to understand protein conformational dynamics and aggregation pathways, and in particular, the effect that small molecu...
Source: Current Opinion in Chemical Biology - January 10, 2018 Category: Biochemistry Authors: Eyers CE, Vonderach M, Ferries S, Jeacock K, Eyers PA Tags: Curr Opin Chem Biol Source Type: research

Ion mobility in the pharmaceutical industry: an established biophysical technique or still niche?
Abstract Over the past decade ion mobility (IM) coupled with mass spectrometry (MS) has emerged as a wide spread analytical technique, utilized in research areas ranging from small molecule to proteins analyzed under native-MS and solution conditions. The ion-neutral collision cross section (Ω) derived from an IM experiment can be used to make inferences about the ion's size, shape and charge distribution, when compared to molecular dynamic (MD) or quantum mechanically (QM) derived candidate structures. IM can also be used as an orthogonal separation technique when coupled with liquid chromatographic (LC) se...
Source: Current Opinion in Chemical Biology - January 4, 2018 Category: Biochemistry Authors: Campuzano ID, Lippens JL Tags: Curr Opin Chem Biol Source Type: research

Activity-based sensing fluorescent probes for iron in biological systems.
Abstract Iron is an essential nutrient for life, and its capacity to cycle between different oxidation states is required for processes spanning oxygen transport and respiration to nucleotide synthesis and epigenetic regulation. However, this same redox ability also makes iron, if not regulated properly, a potentially dangerous toxin that can trigger oxidative stress and damage. New methods that enable monitoring of iron in living biological systems, particularly in labile Fe2+ forms, can help identify its contributions to physiology, aging, and disease. In this review, we summarize recent developments in activity...
Source: Current Opinion in Chemical Biology - January 4, 2018 Category: Biochemistry Authors: Aron AT, Reeves AG, Chang CJ Tags: Curr Opin Chem Biol Source Type: research

Mass spectrometry beyond the native state.
Abstract Native mass spectrometry allows the study of proteins by probing in vacuum the interactions they form in solution. It is a uniquely useful approach for structural biology and biophysics due to the high resolution of separation it affords, allowing the concomitant interrogation of multiple protein components with high mass accuracy. At its most basic, native mass spectrometry reports the mass of intact proteins and the assemblies they form in solution. However, the opportunities for more detailed characterisation are extensive, enabled by the exquisite control of ion motion that is possible in vacuum. Here...
Source: Current Opinion in Chemical Biology - December 27, 2017 Category: Biochemistry Authors: Chandler SA, Benesch JL Tags: Curr Opin Chem Biol Source Type: research

Improving the discovery of secondary metabolite natural products using ion mobility-mass spectrometry.
Abstract Secondary metabolite discovery requires an unbiased, comprehensive workflow to detect unknown unknowns for which little to no molecular knowledge exists. Untargeted mass spectrometry-based metabolomics is a powerful platform, particularly when coupled with ion mobility for high-throughput gas-phase separations to increase peak capacity and obtain gas-phase structural information. Ion mobility data are described by the amount of time an ion spends in the drift cell, which is directly related to an ion's collision cross section (CCS). The CCS parameter describes the size, shape, and charge of a molecule and...
Source: Current Opinion in Chemical Biology - December 26, 2017 Category: Biochemistry Authors: Schrimpe-Rutledge AC, Sherrod SD, McLean JA Tags: Curr Opin Chem Biol Source Type: research

Transaminases for chiral amine synthesis.
Abstract Amine transaminases are important biocatalysts for the synthesis of chiral primary amines. Unlike many enzymes that have been employed for the synthesis of optically active amines, amine transaminases are capable of asymmetric synthesis and do not rely on costly cofactors that must be regenerated in situ. However, their application as general catalysts for the preparation of amines is hampered by a limited substrate scope, substrate and (co)product inhibition and difficulties associated with displacing challenging reaction equilibrium. There has been important progress made to overcome these challenges, i...
Source: Current Opinion in Chemical Biology - December 23, 2017 Category: Biochemistry Authors: Gomm A, O'Reilly E Tags: Curr Opin Chem Biol Source Type: research

Advances in mass spectrometry imaging coupled to ion mobility spectrometry for enhanced imaging of biological tissues.
Abstract Tissues present complex biochemical and morphological composition associated with their various cell types and physiological functions. Mass spectrometry (MS) imaging technologies are powerful tools to investigate the molecular information from biological tissue samples and visualize their complex spatial distributions. Coupling of gas-phase ion mobility spectrometry (IMS) technologies to MS imaging has been increasingly explored to improve performance for biological tissue imaging. This approach allows improved detection of low abundance ions and separation of isobaric molecular species, thus resulting i...
Source: Current Opinion in Chemical Biology - December 21, 2017 Category: Biochemistry Authors: Sans M, Feider CL, Eberlin LS Tags: Curr Opin Chem Biol Source Type: research

Genetically encoded fluorescent sensors for measuring transition and heavy metals in biological systems.
Abstract Great progress has been made in expanding the repertoire of genetically encoded fluorescent sensors for monitoring intracellular transition metals (TMs). This powerful toolkit permits dynamic and non-invasive detection of TMs with high spatial-temporal resolution, which enables us to better understand the roles of TM homeostasis in both physiological and pathological settings. Here we summarize the recent development of genetically encoded fluorescent sensors for intracellular detection of TMs such as zinc and copper, as well as heavy metals including lead, cadmium, mercury, and arsenic. PMID: 292752...
Source: Current Opinion in Chemical Biology - December 21, 2017 Category: Biochemistry Authors: Hao Z, Zhu R, Chen PR Tags: Curr Opin Chem Biol Source Type: research

Biocatalytic reduction of activated CC-bonds and beyond: emerging trends.
Abstract The biocatalytic reduction of activated CC-bonds is dominated by ene-reductases from the Old Yellow Enzyme family, which gained broad practical use owing to exquisite stereoselectivity combined with wide substrate scope. Protein diversity is fostered by mining distinct protein classes and by implementing protein engineering techniques. Recent efforts are focusing on expanding the chemical complexity of the product portfolio, either through substrate functionalization or design of multi-step reactions. This review also highlights unusual chemistries catalyzed by ene-reductases and presents emerging methodo...
Source: Current Opinion in Chemical Biology - December 21, 2017 Category: Biochemistry Authors: Winkler CK, Faber K, Hall M Tags: Curr Opin Chem Biol Source Type: research

Recent advances in enzymatic oxidation of alcohols.
Abstract Enzymatic alcohol oxidation plays an important role in chemical synthesis. In the past two years, new alcohol oxidation enzymes were developed through genome-mining and protein engineering, such as new copper radical oxidases with broad substrate scope, alcohol dehydrogenases with altered cofactor preference and a flavin-dependent alcohol oxidase with enhanced oxygen coupling. New cofactor recycling methods were reported for alcohol dehydrogenase-catalyzed oxidation with photocatalyst and coupled glutaredoxin-glutathione reductase as promising examples. Different alcohol oxidation systems were used for th...
Source: Current Opinion in Chemical Biology - December 16, 2017 Category: Biochemistry Authors: Liu J, Wu S, Li Z Tags: Curr Opin Chem Biol Source Type: research

Contemporary glycomic approaches using ion mobility-mass spectrometry.
Abstract Characterization of complex oligosaccharides has historically required extensive sample handling and separations before analysis using nuclear magnetic resonance spectroscopy and electron impact mass spectra following hydrolysis, derivatization, and gas chromatographic separation. Advances in liquid chromatography separations and tandem mass spectrometry have expanded the range of intact glycan analysis, but carbohydrate structure and conformation-integral chemical characteristics-are often difficult to assess with minimal amounts of sample in a rapid fashion. Because ion mobility spectrometry (IMS) separ...
Source: Current Opinion in Chemical Biology - December 14, 2017 Category: Biochemistry Authors: Morrison KA, Clowers BH Tags: Curr Opin Chem Biol Source Type: research

Functionalization of protein crystals with metal ions, complexes and nanoparticles.
Abstract Self-assembled proteins have specific functions in biology. With inspiration provided by natural protein systems, several artificial protein assemblies have been constructed via site-specific mutations or metal coordination, which have important applications in catalysis, material and bio-supramolecular chemistry. Similar to natural protein assemblies, protein crystals have been recognized as protein assemblies formed of densely-packed monomeric proteins. Protein crystals can be functionalized with metal ions, metal complexes or nanoparticles via soaking, co-crystallization, creating new metal binding sit...
Source: Current Opinion in Chemical Biology - December 12, 2017 Category: Biochemistry Authors: Abe S, Maity B, Ueno T Tags: Curr Opin Chem Biol Source Type: research

Magnifying ion mobility spectrometry-mass spectrometry measurements for biomolecular structure studies.
Abstract Ion mobility spectrometry-mass spectrometry (IMS-MS) provides information about the structures of gas-phase ions in the form of a collision cross section (CCS) with a neutral buffer gas. Indicating relative ion size, a CCS value alone is of limited utility. Although such information can be used to propose different conformer types, finer details of structure are not captured. The increased accessibility of IMS-MS measurements with commercial instrumentation in recent years has ballooned its usage in combination with separate measurements to provide enhanced data from which greater structural inferences ca...
Source: Current Opinion in Chemical Biology - December 11, 2017 Category: Biochemistry Authors: Majuta SN, Maleki H, Kiani Karanji A, Attanyake K, Loch E, Valentine SJ Tags: Curr Opin Chem Biol Source Type: research

Single molecule force spectroscopy: a new tool for bioinorganic chemistry.
Abstract Metalloproteins are essential in biology. The incorporation of metal ion into metalloproteins significantly expands protein functionality and enhances protein stability. Over the last few years, atomic force microscopy-based single molecule force spectroscopy (SMFS) has evolved into a unique tool allowing for probing metalloproteins and metalligand bonds one molecule/bond at a time. Mechanical strength of a wide variety of metalligand bonds has been measured in metal-ligand complexes as well as in metalloproteins, providing detailed information of their underlying free energy profiles and the influence of...
Source: Current Opinion in Chemical Biology - December 6, 2017 Category: Biochemistry Authors: Li H, Zheng P Tags: Curr Opin Chem Biol Source Type: research

Recent advances in lipid separations and structural elucidation using mass spectrometry combined with ion mobility spectrometry, ion-molecule reactions and fragmentation approaches.
Abstract Lipids are a vital class of molecules that play important and varied roles in biological processes, however, fully understanding these roles is extremely difficult due to the immense number and diversity of possible lipid species. While recent advances in chromatography and high resolution mass spectrometry have greatly progressed knowledge about distinct lipid species and functions, effectively separating many lipids still remains problematic. Isomeric lipids have made lipid characterization especially difficult and occur due to subclasses having the same chemical composition, or species having multiple ...
Source: Current Opinion in Chemical Biology - December 6, 2017 Category: Biochemistry Authors: Zheng X, Smith RD, Baker ES Tags: Curr Opin Chem Biol Source Type: research

Collision induced unfolding of isolated proteins in the gas phase: past, present, and future.
Abstract Rapidly characterizing the three-dimensional structures of proteins and the multimeric machines they form remains one of the great challenges facing modern biological and medical sciences. Ion mobility-mass spectrometry based techniques are playing an expanding role in characterizing these functional complexes, especially in drug discovery and development workflows. Despite this expansion, ion mobility-mass spectrometry faces many challenges, especially in the context of detecting small differences in protein tertiary structure that bear functional consequences. Collision induced unfolding is an ion mobil...
Source: Current Opinion in Chemical Biology - December 2, 2017 Category: Biochemistry Authors: Dixit SM, Polasky DA, Ruotolo BT Tags: Curr Opin Chem Biol Source Type: research

Bridging the structural gap of glycoproteomics with ion mobility spectrometry.
Abstract Over the past two decades mass spectrometry (MS) has enabled high throughput studies on the level of a complex proteome. While it has similarly advanced glycobiology, the level of progress has been more restrained. This is in large part due to the diversity and complexity of carbohydrate structures. While MS is now routinely used for glycobiology, it suffers from a critical limitation, that is the inability to resolve isobaric structures. Since so many structurally and functionally distinct carbohydrates are indistinguishable by MS, additional techniques are needed for detailed structural analysis. Ion mo...
Source: Current Opinion in Chemical Biology - December 1, 2017 Category: Biochemistry Authors: Mookherjee A, Guttman M Tags: Curr Opin Chem Biol Source Type: research

Methane to bioproducts: the future of the bioeconomy?
Abstract Methanotrophs have been studied since the 1970s, but interest has increased tremendously in recent years due to their potential to transform methane into valuable bioproducts. The vast quantity of available methane and the low price of methane as natural gas have helped to spur this interest. The most well-studied, biologically-derived products from methane include methanol, polyhydroxyalkanoates, and single cell protein. However, many other high-interest chemicals such as biofuels or high-value products such as ectoine could be made industrially relevant through metabolic engineering. Although challenges...
Source: Current Opinion in Chemical Biology - November 29, 2017 Category: Biochemistry Authors: Pieja AJ, Morse MC, Cal AJ Tags: Curr Opin Chem Biol Source Type: research

Mitochondrial dynamics tracking with iridium(III) complexes.
Abstract Since the discovery of mitochondrial dynamics, demand for dyes able to track this process has been a great. In contrast to static imaging, dynamic tracking requires superior photostability, low cytotoxicity and high resistance to the loss of mitochondrial membrane potential as well as appreciable tolerance to environmental changes. Recently, a variety of phosphorescent Ir(III) complexes have been found to localize in mitochondria and their applications as mitochondrial dynamics trackers have been assessed in cell monolayers, 3D MCSs and live animals. The examples presented here demonstrate that Ir(III) co...
Source: Current Opinion in Chemical Biology - November 22, 2017 Category: Biochemistry Authors: Chen Y, Rees TW, Ji L, Chao H Tags: Curr Opin Chem Biol Source Type: research

Protein lipoylation: an evolutionarily conserved metabolic regulator of health and disease.
Abstract Lipoylation is a rare, but highly conserved lysine posttranslational modification. To date, it is known to occur on only four multimeric metabolic enzymes in mammals, yet these proteins are staples in the core metabolic landscape. The dysregulation of these mitochondrial proteins is linked to a range of human metabolic disorders. Perhaps most striking is that lipoylation itself, the proteins that add or remove the modification, as well as the proteins it decorates are all evolutionarily conserved from bacteria to humans, highlighting the importance of this essential cofactor. Here, we discuss the biologic...
Source: Current Opinion in Chemical Biology - November 20, 2017 Category: Biochemistry Authors: Rowland EA, Snowden CK, Cristea IM Tags: Curr Opin Chem Biol Source Type: research

The application of ion mobility mass spectrometry to metabolomics.
Abstract Mass spectrometry-based metabolomics is being increasingly utilized in various research fields including investigating human diseases, nutrition, industrial applications, and plant/natural products studies. Although new analytical approaches have enhanced the performance of metabolomic analyses, significant challenges associated with throughput, metabolome coverage, and compound identification still exist. Ion mobility mass spectrometry offers great potential for improving throughput and depth of coverage in metabolomics experiments. For example, multi-dimensional, structural resolution offered by ion mob...
Source: Current Opinion in Chemical Biology - November 18, 2017 Category: Biochemistry Authors: Zhang X, Quinn K, Cruickshank-Quinn C, Reisdorph R, Reisdorph N Tags: Curr Opin Chem Biol Source Type: research

Ambient surface mass spectrometry-ion mobility spectrometry of intact proteins.
Abstract Ambient surface mass spectrometry encompasses a broad range of sampling and ionization techniques. To date, only a small subset of these, based on liquid microjunction extraction, have proven suitable for intact protein analysis from thin tissue sections. Liquid extraction surface analysis shows particular promise for this application. Recently, a range of ion mobility spectrometry approaches have been coupled with ambient mass spectrometry. Improvements in signal-to-noise ratios, decreased chemical noise and separation of molecular classes have been described for the analysis of various biological substr...
Source: Current Opinion in Chemical Biology - November 18, 2017 Category: Biochemistry Authors: Griffiths RL, Kocurek KI, Cooper HJ Tags: Curr Opin Chem Biol Source Type: research

(De)hydratases-recent developments and future perspectives.
Abstract Hydratases have gained attention as alternative to chemical catalysts for their ability to add and eliminate water with high regio-selectivity, stereo-selectivity and enantio-selectivity. Recently, especially cofactor-independent hydratases came into research focus as they are of particular interest for industrial application. The investigation of the substrate scope as well as mutagenesis studies combined with high-resolution crystal structures and bioinformatic methods shed light on this promising enzyme class. This review presents latest findings in the field of fatty acid hydratases, linalool dehydrat...
Source: Current Opinion in Chemical Biology - November 17, 2017 Category: Biochemistry Authors: Demming RM, Fischer MP, Schmid J, Hauer B Tags: Curr Opin Chem Biol Source Type: research

Metal complexes promoting catalytic cleavage of nucleic acids-biochemical tools and therapeutics.
Abstract The development of metal complexes that promote degradation of nucleic acids has garnered significant interest as a result of their broad range of potential application. This review focuses on recent progress in the design and synthesis of metal complexes as artificial nucleases that promote either hydrolytic or oxidative cleavage of nucleic acids. Illustrative examples demonstrate the versatility of artificial nucleases for in vitro applications as molecular tools to address biochemical problems, as well as their potential use as therapeutic agents. We also address future challenges for improvement and a...
Source: Current Opinion in Chemical Biology - November 15, 2017 Category: Biochemistry Authors: Yu Z, Cowan JA Tags: Curr Opin Chem Biol Source Type: research

Fundamentals of ion mobility spectrometry.
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...
Source: Current Opinion in Chemical Biology - November 15, 2017 Category: Biochemistry Authors: Gabelica V, Marklund E Tags: Curr Opin Chem Biol Source Type: research

Indirect tRNA aminoacylation during accurate translation and phenotypic mistranslation.
Abstract The fact that most bacteria do not contain a full set of aminoacyl-tRNA synthetases (aaRS) is often underappreciated. In the absence of asparaginyl-tRNA and/or glutaminyl-tRNA synthetase (AsnRS and GlnRS), Asn-tRNA(Asn) and/or Gln-tRNA(Gln) are produced by an indirect tRNA aminoacylation pathway that relies on misacylation of these two tRNAs by two different misacylating aaRSs, followed by transamidation by an amidotransferase (GatCAB in bacteria). This review highlights the central importance of indirect tRNA aminoacylation to accurate protein translation, mechanistic peculiarities that appear to be uniq...
Source: Current Opinion in Chemical Biology - November 15, 2017 Category: Biochemistry Authors: Rathnayake UM, Wood WN, Hendrickson TL Tags: Curr Opin Chem Biol Source Type: research

The potential of Ion Mobility Mass Spectrometry for high-throughput and high-resolution lipidomics.
Abstract Lipids are a large and highly diverse family of biomolecules, which play essential structural, storage and signalling roles in cells and tissues. Although traditional mass spectrometry (MS) approaches used in lipidomics are highly sensitive and selective, lipid analysis remains challenging due to the chemical diversity of lipid structures, multiple isobaric species and incomplete separation using many forms of chromatography. Ion mobility (IM) separates ions in the gas phase based on their physicochemical properties. Addition of IM to the traditional lipidomic workflow both enhances separation of complex ...
Source: Current Opinion in Chemical Biology - November 13, 2017 Category: Biochemistry Authors: Hinz C, Liggi S, Griffin JL Tags: Curr Opin Chem Biol Source Type: research

Biological-inorganic hybrid systems as a generalized platform for chemical production.
Abstract An expanding renewable energy market to supplant petrochemicals has motivated synthesis technologies that use renewable feedstocks, such as CO2. Hybrid biological-inorganic systems provide a sustainable, efficient, versatile, and inexpensive chemical synthesis platform. These systems comprise biocompatible electrodes that transduce electrical energy either directly or indirectly into bioavailable energy, such as H2 and NAD(P)H. In combination, specific bacteria use these energetic reducing equivalents to fix CO2 into multi-carbon organic compounds. As hybrid biological-inorganic technologies have develope...
Source: Current Opinion in Chemical Biology - November 11, 2017 Category: Biochemistry Authors: Nangle SN, Sakimoto KK, Silver PA, Nocera DG Tags: Curr Opin Chem Biol Source Type: research

Advancing the large-scale CCS database for metabolomics and lipidomics at the machine-learning era.
Abstract Metabolomics and lipidomics aim to comprehensively measure the dynamic changes of all metabolites and lipids that are present in biological systems. The use of ion mobility-mass spectrometry (IM-MS) for metabolomics and lipidomics has facilitated the separation and the identification of metabolites and lipids in complex biological samples. The collision cross-section (CCS) value derived from IM-MS is a valuable physiochemical property for the unambiguous identification of metabolites and lipids. However, CCS values obtained from experimental measurement and computational modeling are limited available, wh...
Source: Current Opinion in Chemical Biology - November 11, 2017 Category: Biochemistry Authors: Zhou Z, Tu J, Zhu ZJ Tags: Curr Opin Chem Biol Source Type: research

Anticancer metal-N-heterocyclic carbene complexes of gold, platinum and palladium.
Abstract Transition metal compounds are a rich source for anticancer drug development. Judicious application of coordination ligands is a critical success factor in the design of effective anti-tumor compounds. N-heterocyclic carbenes (NHC) are stable ligands that have strong donor strengths in stabilizing metal ions and versatility in structural modifications to provide diverse scaffolds for biological molecular targeting. Remarkable advances have been achieved in the development of metal NHC complexes as anticancer as well as theranostic agents. NHC complexes of gold, platinum and palladium have been designed to...
Source: Current Opinion in Chemical Biology - November 10, 2017 Category: Biochemistry Authors: Zou T, Lok CN, Wan PK, Zhang ZF, Fung SK, Che CM Tags: Curr Opin Chem Biol Source Type: research

Carboxylic acid reductase enzymes (CARs).
Abstract Carboxylate reductases (CARs) are emerging as valuable catalysts for the selective one-step reduction of carboxylic acids to their corresponding aldehydes. The substrate scope of CARs is exceptionally broad and offers potential for their application in diverse synthetic processes. Two major fields of application are the preparation of aldehydes as end products for the flavor and fragrance sector and the integration of CARs in cascade reactions with aldehydes as the key intermediates. The latest applications of CARs are dominated by in vivo cascades and chemo-enzymatic reaction sequences. The challenge to ...
Source: Current Opinion in Chemical Biology - November 8, 2017 Category: Biochemistry Authors: Winkler M Tags: Curr Opin Chem Biol Source Type: research

Metabolic engineering of yeast for lignocellulosic biofuel production.
Abstract Production of biofuels from lignocellulosic biomass remains an unsolved challenge in industrial biotechnology. Efforts to use yeast for conversion face the question of which host organism to use, counterbalancing the ease of genetic manipulation with the promise of robust industrial phenotypes. Saccharomyces cerevisiae remains the premier host for metabolic engineering of biofuel pathways, due to its many genetic, systems and synthetic biology tools. Numerous engineering strategies for expanding substrate ranges and diversifying products of S. cerevisiae have been developed. Other yeasts generally lack th...
Source: Current Opinion in Chemical Biology - November 8, 2017 Category: Biochemistry Authors: Jin YS, Cate JH Tags: Curr Opin Chem Biol Source Type: research

The application of ion-mobility mass spectrometry for structure/function investigation of protein complexes.
Abstract Ion-mobility mass spectrometry (IM-MS) is an approach that can provide information on the stoichiometry, composition, protein contacts and topology of protein complexes. The power of this approach lies not only in its sensitivity and speed of analysis, but also in the fact that it is a technique that can capture the repertoire of conformational states adopted by protein assemblies. Here, we describe the array of available IM-MS based tools, and demonstrate their application to the structural characterization of various protein complexes, including challenging systems as amyloid aggregates and membrane pro...
Source: Current Opinion in Chemical Biology - November 8, 2017 Category: Biochemistry Authors: Ben-Nissan G, Sharon M Tags: Curr Opin Chem Biol Source Type: research

Epitranscriptomics: regulation of mRNA metabolism through modifications.
Abstract Cellular RNAs can be modified post-transcriptionally with dynamic and reversible chemical modifications. These modifications can alter the structure and metabolism of mRNA, but only recent methodological and conceptual advances allowed systematic mapping and functional analysis to unfold the role they play in mRNA biology. Mapping the most common internal mRNA modification, N(6)-methyladenosine (m(6)A), paved the way for the deciphering of other types of mRNA modifications, such as N(1)-methyladenosine (m(1)A). RNA methylation provides dynamic regulation to the processing, export, translation and stabilit...
Source: Current Opinion in Chemical Biology - November 7, 2017 Category: Biochemistry Authors: Peer E, Rechavi G, Dominissini D Tags: Curr Opin Chem Biol Source Type: research

Overcoming the energetic limitations of syngas fermentation.
Abstract The fermentation of synthesis gas (including carbon monoxide, carbon dioxide, and hydrogen) with anaerobic acetogens is an established biotechnological process that has recently been transferred to a commercial scale. The natural product spectrum of acetogens is natively restricted to acetate, ethanol, and 2,3-butanediol but is rapidly expanding to heterologous products. Syngas fermentation can achieve high carbon-efficiencies; however, the underlying metabolism is operating at a thermodynamic limit. This necessitates special enzymatic properties for energy conservation by acetogens. Therefore, the availa...
Source: Current Opinion in Chemical Biology - November 6, 2017 Category: Biochemistry Authors: Molitor B, Marcellin E, Angenent LT Tags: Curr Opin Chem Biol Source Type: research

Structure-based mechanistic insights into catalysis by small self-cleaving ribozymes.
Abstract Small self-cleaving ribozymes are widely distributed in nature and are essential for rolling-circle-based replication of satellite and pathogenic RNAs. Earlier structure-function studies on the hammerhead, hairpin, glmS, hepatitis delta virus and Varkud satellite ribozymes have provided insights into their overall architecture, their catalytic active site organization, and the role of nearby nucleobases and hydrated divalent cations in facilitating general acid-base and electrostatic-mediated catalysis. This review focuses on recent structure-function research on active site alignments and catalytic mecha...
Source: Current Opinion in Chemical Biology - November 3, 2017 Category: Biochemistry Authors: Ren A, Micura R, Patel DJ Tags: Curr Opin Chem Biol Source Type: research

Glycan analysis by ion mobility-mass spectrometry and gas-phase spectroscopy.
Abstract Due to the existence of numerous isomers, the in-depth analysis of glycans represents a major challenge. Currently, the majority of glycans are analysed using mass spectrometry (MS)-based techniques, which can provide information on regioisomers but usually fail to differentiate stereoisomers. A promising approach to overcome this limitation is to implement ion mobility spectrometry (IMS) as an additional gas-phase separation dimension. This review highlights recent developments in which IM-MS was used as a tool for comprehensive glycan analysis or as rapid screening method for glycan feature analysis. Fu...
Source: Current Opinion in Chemical Biology - November 3, 2017 Category: Biochemistry Authors: Manz C, Pagel K Tags: Curr Opin Chem Biol Source Type: research

Lignocellulose deconstruction in the biosphere.
Abstract Microorganisms have evolved different and yet complementary mechanisms to degrade biomass in the biosphere. The chemical biology of lignocellulose deconstruction is a complex and intricate process that appears to vary in response to specific ecosystems. These microorganisms rely on simple to complex arrangements of glycoside hydrolases to conduct most of these polysaccharide depolymerization reactions and also, as discovered more recently, oxidative mechanisms via lytic polysaccharide monooxygenases or non-enzymatic Fenton reactions which are used to enhance deconstruction. It is now clear that these deco...
Source: Current Opinion in Chemical Biology - October 31, 2017 Category: Biochemistry Authors: Bomble YJ, Lin CY, Amore A, Wei H, Holwerda EK, Ciesielski PN, Donohoe BS, Decker SR, Lynd LR, Himmel ME Tags: Curr Opin Chem Biol Source Type: research

Synthesis of chiral amines using redox biocatalysis.
Abstract Chiral amines feature in a large number of small molecule pharmaceuticals, and thus methods for their asymmetric synthesis are of considerable interest. Biocatalytic approaches have come to the fore in recent years as these offer advantages of superior atom economy, mild reaction conditions and excellent stereoselectivity. Advances in redox cofactor process technology have meant that oxidoreductase enzymes in particular now have growing potential as industrial catalysts for amine formation. In this review we survey recent developments in the discovery and application of oxidoreductase enzymes for amine pr...
Source: Current Opinion in Chemical Biology - October 31, 2017 Category: Biochemistry Authors: Grogan G Tags: Curr Opin Chem Biol Source Type: research

Modern methods for laboratory diversification of biomolecules.
Abstract Genetic variation fuels Darwinian evolution, yet spontaneous mutation rates are maintained at low levels to ensure cellular viability. Low mutation rates preclude the exhaustive exploration of sequence space for protein evolution and genome engineering applications, prompting scientists to develop methods for efficient and targeted diversification of nucleic acid sequences. Directed evolution of biomolecules relies upon the generation of unbiased genetic diversity to discover variants with desirable properties, whereas genome-engineering applications require selective modifications on a genomic scale with...
Source: Current Opinion in Chemical Biology - October 30, 2017 Category: Biochemistry Authors: Bratulic S, Badran AH Tags: Curr Opin Chem Biol Source Type: research

Recent progress in dissecting molecular recognition by DNA polymerases with non-native substrates.
Abstract DNA polymerases must discriminate the correct Watson-Crick base pair-forming deoxynucleoside triphosphate (dNTP) substrate from three other dNTPs and additional triphosphates found in the cell. The rarity of misincorporations in vivo, then, belies the high tolerance for dNTP analogs observed in vitro. Advances over the last 10 years in single-molecule fluorescence and electronic detection of dNTP analog incorporation enable exploration of the mechanism and limits to base discrimination by DNA polymerases. Such studies reveal transient motions of DNA polymerase during substrate recognition and mutagenesis ...
Source: Current Opinion in Chemical Biology - October 27, 2017 Category: Biochemistry Authors: Pugliese KM, Weiss GA Tags: Curr Opin Chem Biol Source Type: research

Recent advances in ion mobility-mass spectrometry for improved structural characterization of glycans and glycoconjugates.
Abstract Glycans and glycoconjugates are involved in regulating a vast array of cellular and molecular processes. Despite the importance of glycans in biology and disease, characterization of glycans remains difficult due to their structural complexity and diversity. Mass spectrometry (MS)-based techniques have emerged as the premier analytical tools for characterizing glycans. However, traditional MS-based strategies struggle to distinguish the large number of coexisting isomeric glycans that are indistinguishable by mass alone. Because of this, ion mobility spectrometry coupled to MS (IM-MS) has received conside...
Source: Current Opinion in Chemical Biology - October 25, 2017 Category: Biochemistry Authors: Chen Z, Glover MS, Li L Tags: Curr Opin Chem Biol Source Type: research

Evolution of epigenetic chromatin states.
SJ Abstract The central dogma of gene expression entails the flow of genetic information from DNA to RNA, then to protein. Decades of studies on epigenetics have characterized an additional layer of information, where epigenetic states help to shape differential utilization of genetic information. Orchestrating conditional gene expressions to elicit a defined phenotype and function, epigenetics states distinguish different cell types or maintain a long-lived memory of past signals. Packaging the genetic information in the nucleus of the eukaryotic cell, chromatin provides a large regulatory repertoire that capaci...
Source: Current Opinion in Chemical Biology - October 24, 2017 Category: Biochemistry Authors: Yung PYK, Elsässer SJ Tags: Curr Opin Chem Biol Source Type: research

Mutations in RNA methylating enzymes in disease.
Abstract RNA methylation is an abundant modification identified in various RNA species in both prokaryotic and eukaryotic organisms. However, the functional roles for the majority of these methylations remain largely unclear. In eukaryotes, many RNA methylations have been suggested to participate in fundamental cellular processes. Mutations in eukaryotic RNA methylating enzymes, and a consequent change in methylation, can lead to the development of diseases and disorders. In contrast, loss of RNA methylation in prokaryotes can be beneficial to microorganisms, especially under antibiotic pressure. Here we discuss s...
Source: Current Opinion in Chemical Biology - October 20, 2017 Category: Biochemistry Authors: Stojković V, Fujimori DG Tags: Curr Opin Chem Biol Source Type: research