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Current Opinion in Chemical Biology

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https://www.readbyqxmd.com/read/28092796/global-open-data-management-in-metabolomics
#1
REVIEW
Kenneth Haug, Reza M Salek, Christoph Steinbeck
Chemical Biology employs chemical synthesis, analytical chemistry and other tools to study biological systems. Recent advances in both molecular biology such as next generation sequencing (NGS) have led to unprecedented insights towards the evolution of organisms' biochemical repertoires. Because of the specific data sharing culture in Genomics, genomes from all kingdoms of life become readily available for further analysis by other researchers. While the genome expresses the potential of an organism to adapt to external influences, the Metabolome presents a molecular phenotype that allows us to asses the external influences under which an organism exists and develops in a dynamic way...
January 13, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28088696/cell-selective-proteomics-for-biological-discovery
#2
REVIEW
Shannon E Stone, Weslee S Glenn, Graham D Hamblin, David A Tirrell
Cells alter the proteome to respond to environmental and developmental cues. Global analysis of proteomic responses is of limited value in heterogeneous environments, where there is no 'average' cell. Advances in sequencing, protein labeling, mass spectrometry, and data analysis have fueled recent progress in the investigation of specific subpopulations of cells in complex systems. Here we highlight recently developed chemical tools that enable cell-selective proteomic analysis of complex biological systems, from bacterial pathogens to whole animals...
January 12, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28088695/deep-metabolome-annotation-in-natural-products-research-towards-a-virtuous-cycle-in-metabolite-identification
#3
REVIEW
Pierre-Marie Allard, Grégory Genta-Jouve, Jean-Luc Wolfender
Natural products (NPs) research is changing and rapidly adopting cutting-edge tools, which radically transform the way to characterize extracts and small molecules. With the innovations in metabolomics, early integration of deep metabolome annotation information allows to efficiently guide the isolation of valuable NPs only and, in parallel, to generate massive metadata sets for the study of given extracts under various perspectives. This is the case for chemotaxonomy studies where common biosynthetic traits among species can be evidenced, but also for drug discovery purpose where such traits, in combination with bioactivity studies on extracts, may evidence bioactive molecules even before their isolation...
January 12, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28088694/metabolic-network-modeling-with-model-organisms
#4
REVIEW
L Safak Yilmaz, Albertha Jm Walhout
Flux balance analysis (FBA) with genome-scale metabolic network models (GSMNM) allows systems level predictions of metabolism in a variety of organisms. Different types of predictions with different accuracy levels can be made depending on the applied experimental constraints ranging from measurement of exchange fluxes to the integration of gene expression data. Metabolic network modeling with model organisms has pioneered method development in this field. In addition, model organism GSMNMs are useful for basic understanding of metabolism, and in the case of animal models, for the study of metabolic human diseases...
January 12, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28086192/from-single-cells-to-our-planet-recent-advances-in-using-mass-spectrometry-for-spatially-resolved-metabolomics
#5
REVIEW
Daniel Petras, Alan K Jarmusch, Pieter C Dorrestein
Spatial information in the form of 3D digital content has been increasingly integrated into our daily lives. Metabolomic studies parallel this trend with spatial and time resolved information being acquired. Mass spectrometry imaging (MSI), which combines qualitative and quantitative molecular information with spatial information, plays a crucial role in mass spectrometry-based metabolomics. The lateral spatial resolution obtained by MSI continues to improve and allows mass spectrometers to be used as molecular microscopes-enabling the exploration of the cellular and subcellular metabolome...
January 10, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28064089/frontiers-of-high-throughput-metabolomics
#6
REVIEW
Mattia Zampieri, Karthik Sekar, Nicola Zamboni, Uwe Sauer
Large scale metabolomics studies are increasingly used to investigate genetically different individuals and time-dependent responses to environmental stimuli. New mass spectrometric approaches with at least an order of magnitude more rapid analysis of small molecules within the cell's metabolome are now paving the way towards true high-throughput metabolomics, opening new opportunities in systems biology, functional genomics, drug discovery, and personalized medicine. Here we discuss the impact and advantages of the progress made in profiling large cohorts and dynamic systems with high temporal resolution and automated sampling...
January 5, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28040658/developing-drugs-targeting-transition-metal-homeostasis
#7
REVIEW
Claire M Weekley, Chuan He
Metal dyshomeostasis is involved in the pathogenesis and progression of diseases including cancer and neurodegenerative diseases. Metal chelators and ionophores are well known modulators of transition metal homeostasis, and a number of these molecules are in clinical trials. Metal-binding compounds are not the only drugs capable of targeting transition metal homeostasis. This review presents recent highlights in the development of chelators and ionophores for the treatment of cancer and neurodegenerative disease...
December 29, 2016: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28038349/imine-reductases-ireds
#8
REVIEW
Juan Mangas-Sanchez, Scott P France, Sarah L Montgomery, Godwin A Aleku, Henry Man, Mahima Sharma, Jeremy I Ramsden, Gideon Grogan, Nicholas J Turner
Imine reductases (IREDs) have emerged as a valuable new set of biocatalysts for the asymmetric synthesis of optically active amines. The development of bioinformatics tools and searchable databases has led to the identification of a diverse range of new IRED biocatalysts that have been characterised and employed in different synthetic processes. This review describes the latest developments in the structural and mechanistic aspects of IREDs, together with synthetic applications of these enzymes, and identifies ongoing and future challenges in the field...
December 27, 2016: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28025166/considerations-when-choosing-a-genetic-model-organism-for-metabolomics-studies
#9
REVIEW
Laura K Reed, Charles F Baer, Arthur S Edison
Model organisms are important in many areas of chemical biology. In metabolomics, model organisms can provide excellent samples for methods development as well as the foundation of comparative phylometabolomics, which will become possible as metabolomics applications expand. Comparative studies of conserved and unique metabolic pathways will help in the annotation of metabolites as well as provide important new targets of investigation in biology and biomedicine. However, most chemical biologists are not familiar with genetics, which needs to be considered when choosing a model organism...
December 22, 2016: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28025165/searching-molecular-structure-databases-using-tandem-ms-data-are-we-there-yet
#10
REVIEW
Sebastian Böcker
Untargeted metabolomics experiments usually rely on tandem mass spectrometry (MS/MS) to identify the thousands of compounds in a complex sample. Spectral libraries used for identification are incomplete, and many metabolites remain unknown. There has been a recent development to replace spectral libraries by molecular structure databases when searching the MS/MS data of the unknown compound. Several tools have been developed for this task, including CFM-ID, MetFrag, MAGMa(+), FingerID and CSI:FingerID. These methods are already helpful for everyday metabolomics; with further advances, these methods can become indispensable tools for tomorrow's metabolomics...
December 22, 2016: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/27992799/metal-homeostasis-in-infectious-disease-recent-advances-in-bacterial-metallophores-and-the-human-metal-withholding-response
#11
REVIEW
Wilma Neumann, Anmol Gulati, Elizabeth M Nolan
A tug-of-war between the mammalian host and bacterial pathogen for nutrients, including first-row transition metals (e.g. Mn, Fe, Zn), occurs during infection. Here we present recent advances about three metal-chelating metabolites that bacterial pathogens deploy when invading the host: staphylopine, staphyloferrin B, and enterobactin. These highlights provide new insights into the mechanisms of bacterial metal acquisition and regulation, as well as the contributions of host-defense proteins during the human innate immune response...
December 16, 2016: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/27992798/peroxygenases-en-route-to-becoming-dream-catalysts-what-are-the-opportunities-and-challenges
#12
REVIEW
Yonghua Wang, Dongming Lan, Rabia Durrani, Frank Hollmann
Peroxygenases are promising catalysts for preparative oxyfunctionalization chemistry as they combine the versatility of P450 monooxygenases with simplicity of cofactor-independent enzymes. Though many interesting applications have been reported, today 'we have only scratched the surface' and significant efforts are necessary to solve issues related to selectivity of the wild type enzymes and low product titers. For this, further elucidation of the vast natural diversity as well as protein and reaction engineering approaches are discussed...
December 16, 2016: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/27978999/editorial-overview-biofuels-at-the-crossroads
#13
EDITORIAL
David Savage, Wenjun Zhang
No abstract text is available yet for this article.
December 2016: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/27768949/biofuel-metabolic-engineering-with-biosensors
#14
REVIEW
Stacy-Anne Morgan, Dana C Nadler, Rayka Yokoo, David F Savage
Metabolic engineering offers the potential to renewably produce important classes of chemicals, particularly biofuels, at an industrial scale. DNA synthesis and editing techniques can generate large pathway libraries, yet identifying the best variants is slow and cumbersome. Traditionally, analytical methods like chromatography and mass spectrometry have been used to evaluate pathway variants, but such techniques cannot be performed with high throughput. Biosensors - genetically encoded components that actuate a cellular output in response to a change in metabolite concentration - are therefore a promising tool for rapid and high-throughput evaluation of candidate pathway variants...
December 2016: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/27768948/biocatalysts-for-methane-conversion-big-progress-on-breaking-a-small-substrate
#15
REVIEW
Thomas J Lawton, Amy C Rosenzweig
Nature utilizes two groups of enzymes to catalyze methane conversions, methyl-coenzyme M reductases (MCRs) and methane monooxygenases (MMOs). These enzymes have been difficult to incorporate into industrial processes due to their complexity, poor stability, and lack of recombinant tractability. Despite these issues, new ways of preparing and stabilizing these enzymes have recently been discovered, and new mechanistic insight into how MCRs and MMOs break the C-H bond in nature's most inert hydrocarbon have been obtained...
December 2016: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/27736648/applied-evolutionary-theories-for-engineering-of-secondary-metabolic-pathways
#16
REVIEW
Brian O Bachmann
An expanded definition of 'secondary metabolism' is emerging. Once the exclusive provenance of naturally occurring organisms, evolved over geological time scales, secondary metabolism increasingly encompasses molecules generated via human engineered biocatalysts and biosynthetic pathways. Many of the tools and strategies for enzyme and pathway engineering can find origins in evolutionary theories. This perspective presents an overview of selected proposed evolutionary strategies in the context of engineering secondary metabolism...
December 2016: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/27697701/non-natural-carbenoid-and-nitrenoid-insertion-reactions-catalyzed-by-heme-proteins
#17
REVIEW
Joshua G Gober, Eric M Brustad
Despite increasing interest in using enzymes as tools for synthesis, many reactions discovered through the creativity of synthetic chemists remain beyond the scope of biocatalysis. This vacancy in the field has compelled researchers to develop strategies to adapt protein scaffolds for new reactivity. Heme proteins have recently been shown to activate synthetic precursors to generate reactive metallocarbenoid and metallonitrenoid species that enable the biosynthetic construction of novel C-C, C-N, and other bonds using mechanisms not previously explored by Nature...
December 2016: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/27697700/mechanistic-insights-into-diels-alder-reactions-in-natural-product-biosynthesis
#18
REVIEW
Takuya Hashimoto, Tomohisa Kuzuyama
Natural enzymes that catalyze Diels-Alder reactions have long been sought after, yet few enzymes have been experimentally confirmed to perform this reaction. In the past five years, several stand-alone enzymes that can catalyze the Diels-Alder reaction had been identified and characterized. Among which, the crystal structures of SpnF, PyrI4 and AbyU have been determined. The structures of PyrI4 and AbyU, which are involved in spirotetronate/spirotetramate biosynthesis, are particularly informative since they shed light on how a natural catalyst captures the flexible substrate and facilitates the intramolecular Diels-Alder reaction through stabilization of the transition state in catalysis...
December 2016: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/27693891/convergent-biosynthetic-pathways-to-%C3%AE-lactam-antibiotics
#19
REVIEW
Craig A Townsend
Five naturally-occurring families of β-lactams have inspired a class of drugs that constitute >60% of the antimicrobials used in human medicine. Their biosynthetic pathways reveal highly individualized synthetic strategies that yet converge on a common azetidinone ring assembled in structural contexts that confer selective binding and inhibition of d,d-transpeptidases that play essential roles in bacterial cell wall (peptidoglycan) biosynthesis. These enzymes belong to a single 'clan' of evolutionarily distinct serine hydrolases whose active site geometry and mechanism of action is specifically matched by these antibiotics for inactivation that is kinetically competitive with their native function...
December 2016: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/27693890/photorespiration-and-the-potential-to-improve-photosynthesis
#20
REVIEW
Martin Hagemann, Hermann Bauwe
The photorespiratory pathway, in short photorespiration, is an essential metabolite repair pathway that allows the photosynthetic CO2 fixation of plants to occur in the presence of oxygen. It is necessary because oxygen is a competing substrate of the CO2-fixing enzyme ribulose 1,5-bisphosphate carboxylase, forming 2-phosphoglycolate that negatively interferes with photosynthesis. Photorespiration very efficiently recycles 2-phosphoglycolate into 3-phosphoglycerate, which re-enters the Calvin-Benson cycle to drive sustainable photosynthesis...
December 2016: Current Opinion in Chemical Biology
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