Cell-selective proteomics for biological discovery.
Abstract 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. PMID: 28088696 [PubMed - as supplied by publisher]...
Source: Current Opinion in Chemical Biology - January 12, 2017 Category: Biochemistry Authors: Stone SE, Glenn WS, Hamblin GD, Tirrell DA Tags: Curr Opin Chem Biol Source Type: research

From single cells to our planet-recent advances in using mass spectrometry for spatially resolved metabolomics.
Abstract 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. Towards the ot...
Source: Current Opinion in Chemical Biology - January 10, 2017 Category: Biochemistry Authors: Petras D, Jarmusch AK, Dorrestein PC Tags: Curr Opin Chem Biol Source Type: research

Frontiers of high-throughput metabolomics.
Abstract 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...
Source: Current Opinion in Chemical Biology - January 5, 2017 Category: Biochemistry Authors: Zampieri M, Sekar K, Zamboni N, Sauer U Tags: Curr Opin Chem Biol Source Type: research

Developing drugs targeting transition metal homeostasis.
Abstract 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. Moreover, we discuss the development of small molecules that alter copper and iron homeostasi...
Source: Current Opinion in Chemical Biology - December 29, 2016 Category: Biochemistry Authors: Weekley CM, He C Tags: Curr Opin Chem Biol Source Type: research

Imine reductases (IREDs).
Abstract 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. PMID: 28038349 [PubMed - as supplied by publish...
Source: Current Opinion in Chemical Biology - December 27, 2016 Category: Biochemistry Authors: Mangas-Sanchez J, France SP, Montgomery SL, Aleku GA, Man H, Sharma M, Ramsden JI, Grogan G, Turner NJ Tags: Curr Opin Chem Biol Source Type: research

Searching molecular structure databases using tandem MS data: are we there yet?
r S Abstract 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 ca...
Source: Current Opinion in Chemical Biology - December 22, 2016 Category: Biochemistry Authors: Böcker S Tags: Curr Opin Chem Biol Source Type: research

Considerations when choosing a genetic model organism for metabolomics studies.
Abstract 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. In this review we...
Source: Current Opinion in Chemical Biology - December 22, 2016 Category: Biochemistry Authors: Reed LK, Baer CF, Edison AS Tags: Curr Opin Chem Biol Source Type: research

Peroxygenases en route to becoming dream catalysts. What are the opportunities and challenges?
Abstract 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. PMID: 27992798 [PubMed - as supplied by publisher] (Source: Cu...
Source: Current Opinion in Chemical Biology - December 16, 2016 Category: Biochemistry Authors: Wang Y, Lan D, Durrani R, Hollmann F Tags: Curr Opin Chem Biol Source Type: research

Metal homeostasis in infectious disease: recent advances in bacterial metallophores and the human metal-withholding response.
Abstract 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. The studies also underscore that the chemical composition of the microenvi...
Source: Current Opinion in Chemical Biology - December 16, 2016 Category: Biochemistry Authors: Neumann W, Gulati A, Nolan EM Tags: Curr Opin Chem Biol Source Type: research

Editorial Overview. Biofuels: At the crossroads.
PMID: 27978999 [PubMed - in process] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - December 1, 2016 Category: Biochemistry Authors: Savage D, Zhang W Tags: Curr Opin Chem Biol Source Type: research

Biocatalysts for methane conversion: big progress on breaking a small substrate.
Abstract 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. This review focuses on recent findings in the methane biocatalysis field, and discusse...
Source: Current Opinion in Chemical Biology - October 18, 2016 Category: Biochemistry Authors: Lawton TJ, Rosenzweig AC Tags: Curr Opin Chem Biol Source Type: research

Biofuel metabolic engineering with biosensors.
Abstract 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 promisin...
Source: Current Opinion in Chemical Biology - October 18, 2016 Category: Biochemistry Authors: Morgan SA, Nadler DC, Yokoo R, Savage DF Tags: Curr Opin Chem Biol Source Type: research

Editorial overview: Chemistry for biopolymers to investigate and even move beyond nature.
PMID: 27751659 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - October 14, 2016 Category: Biochemistry Authors: Pentelute BL, Wang L Tags: Curr Opin Chem Biol Source Type: research

Applied evolutionary theories for engineering of secondary metabolic pathways.
Abstract 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. In addition to the wealth of biocatalysts provided via secondary metabolic p...
Source: Current Opinion in Chemical Biology - October 10, 2016 Category: Biochemistry Authors: Bachmann BO Tags: Curr Opin Chem Biol Source Type: research

Structural insight into the necessary conformational changes of modular nonribosomal peptide synthetases.
Abstract Nonribosomal peptide synthetases (NRPSs) catalyze the assembly line biosynthesis of peptide natural products that play important roles in microbial signaling and communication. These multidomain enzymes use an integrated carrier protein that delivers the growing peptide to the catalytic domains, requiring coordinated conformational changes that allow the proper sequence of synthetic steps. Recent structural studies of NRPSs have described important conformational states and illustrate the critical role of a small subdomain within the adenylation domains. This subdomain alternates between catalytic conform...
Source: Current Opinion in Chemical Biology - September 24, 2016 Category: Biochemistry Authors: Gulick AM Tags: Curr Opin Chem Biol Source Type: research

Engineered transmembrane pores.
Abstract Today, hundreds of researchers are working on nanopores, making an impact in both basic science and biotechnology. Proteins remain the most versatile sources of nanopores, based on our ability to engineer them with sub-nanometer precision. Recent work aimed at the construction and discovery of novel pores has included unnatural amino acid mutagenesis and the application of selection techniques. The diversity of structures has now been increased through the development of helix-based pores as well as the better-known β barrels. New developments also include truncated pores, which pierce bilayers throu...
Source: Current Opinion in Chemical Biology - September 19, 2016 Category: Biochemistry Authors: Ayub M, Bayley H Tags: Curr Opin Chem Biol Source Type: research

Editorial overview: Synthetic biology - From understanding to engineering biology and back.
PMID: 27648970 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - September 17, 2016 Category: Biochemistry Authors: Bange G, Waldminghaus T Tags: Curr Opin Chem Biol Source Type: research

Engineered knottin peptides as diagnostics, therapeutics, and drug delivery vehicles.
Abstract Inhibitor cystine-knots, also known as knottins, are a structural family of ultra-stable peptides with diverse functions. Knottins and related backbone-cyclized peptides called cyclotides contain three disulfide bonds connected in a particular arrangement that endows these peptides with high thermal, proteolytic, and chemical stability. Knottins have gained interest as candidates for non-invasive molecular imaging and for drug development as they can possess the pharmacological properties of small molecules and the target affinity and selectively of protein biologics. Naturally occurring knottins are clin...
Source: Current Opinion in Chemical Biology - September 16, 2016 Category: Biochemistry Authors: Kintzing JR, Cochran JR Tags: Curr Opin Chem Biol Source Type: research

Molecular tools for acute spatiotemporal manipulation of signal transduction.
Abstract The biochemical activities involved in signal transduction in cells are under tight spatiotemporal regulation. To study the effects of the spatial patterning and temporal dynamics of biochemical activities on downstream signaling, researchers require methods to manipulate signaling pathways acutely and rapidly. In this review, we summarize recent developments in the design of three broad classes of molecular tools for perturbing signal transduction, classified by their type of input signal: chemically induced, optically induced, and magnetically induced. PMID: 27639090 [PubMed - as supplied by publis...
Source: Current Opinion in Chemical Biology - September 14, 2016 Category: Biochemistry Authors: Ross B, Mehta S, Zhang J Tags: Curr Opin Chem Biol Source Type: research

Mechanisms of cyanobactin biosynthesis.
Abstract Cyanobactins are a diverse collection of natural products that originate from short peptides made on a ribosome. The amino acids are modified in a series of transformations catalyzed by multiple enzymes. The patellamide pathway is the most well studied and characterized example. Here we review the structures and mechanisms of the enzymes that cleave peptide bonds, macrocyclise peptides, heterocyclise cysteine (as well as threonine and serine) residues, oxidize five-membered heterocycles and attach prenyl groups. Some enzymes operate by novel mechanisms which is of interest and in addition the enzymes unco...
Source: Current Opinion in Chemical Biology - September 14, 2016 Category: Biochemistry Authors: Czekster CM, Ge Y, Naismith JH Tags: Curr Opin Chem Biol Source Type: research

Mechanistic insights into class B radical-S-adenosylmethionine methylases: ubiquitous tailoring enzymes in natural product biosynthesis.
Abstract Class B radical S-adenosylmethionine (SAM) methylases are notable for their ability to catalyse methylation reactions in the biosynthesis of a wide variety of natural products, including polyketides, ribosomally biosynthesised and post-translationally modified peptides (RiPPs), nonribosomal peptides (NRPs), aminoglycosides, β-lactams, phosphonates, enediynes, aminocoumarins and terpenes. Here, we discuss the diversity of substrates and catalytic mechanism utilised by such enzymes, highlighting the stereochemical course of methylation reactions at un-activated carbon centres and the ability of some me...
Source: Current Opinion in Chemical Biology - September 12, 2016 Category: Biochemistry Authors: Zhou S, Alkhalaf LM, de Los Santos EL, Challis GL Tags: Curr Opin Chem Biol Source Type: research

Mechanisms of β-amino acid incorporation in polyketide macrolactam biosynthesis.
Mechanisms of β-amino acid incorporation in polyketide macrolactam biosynthesis. Curr Opin Chem Biol. 2016 Sep 9;35:58-64 Authors: Miyanaga A, Kudo F, Eguchi T Abstract Macrolactam antibiotics are an important class of macrocyclic polyketides. In recent years, the number of identified β-amino acid-containing macrolactams and their biosynthetic gene clusters have greatly expanded. Functional analyses of vicenistatin biosynthetic enzymes have revealed conserved biosynthetic machinery that incorporates a β-amino acid starter unit into the polyketide skeleton. A VinN-type adenylation enzyme...
Source: Current Opinion in Chemical Biology - September 9, 2016 Category: Biochemistry Authors: Miyanaga A, Kudo F, Eguchi T Tags: Curr Opin Chem Biol Source Type: research

Clostridia: a flexible microbial platform for the production of alcohols.
Abstract Solventogenic clostridia are native producers of ethanol and many higher alcohols employing a broad range of cheap renewable substrates, such as lignocellulosic materials and C1 gases (CO and CO2). These characteristics enable solventogenic clostridia to act as flexible microbial platforms for the production of liquid biofuels. With the rapid development of genetic tools in recent years, the intrinsic intractability of clostridia has been largely overcome, thus, engineering clostridia for production of chemicals and fuels has attracted increasing interests. Here, we provide an overview of recent progress ...
Source: Current Opinion in Chemical Biology - September 9, 2016 Category: Biochemistry Authors: Ren C, Wen Z, Xu Y, Jiang W, Gu Y Tags: Curr Opin Chem Biol Source Type: research

Designing sugar mimetics: non-natural pyranosides as innovative chemical tools.
Abstract The importance of oligosaccharides in myriad biological processes is becoming increasingly clear. However, these carbohydrate-mediated processes are often challenging to dissect due to the often poor affinity, stability and selectivity of the oligosaccharides involved. To circumvent these issues, non-natural carbohydrates-carbohydrate mimics-are being designed as innovative tools to modify biomolecules of interest or to understand biological pathways using fluorescence microscopy, X-ray or nuclear magnetic resonance spectroscopy (NMR). This review focuses on key examples of recently developed non-natural ...
Source: Current Opinion in Chemical Biology - September 9, 2016 Category: Biochemistry Authors: Saliba RC, Pohl NL Tags: Curr Opin Chem Biol Source Type: research

Cyanobacterial metabolic engineering for biofuel and chemical production.
Abstract Rising levels of atmospheric CO2 are contributing to the global greenhouse effect. Large scale use of atmospheric CO2 may be a sustainable and renewable means of chemical and liquid fuel production to mitigate global climate change. Photosynthetic organisms are an ideal platform for efficient, natural CO2 conversion to a broad range of chemicals. Cyanobacteria are especially attractive for these purposes, due to their genetic malleability and relatively fast growth rate. Recent years have yielded a range of work in the metabolic engineering of cyanobacteria and have led to greater knowledge of the host me...
Source: Current Opinion in Chemical Biology - September 7, 2016 Category: Biochemistry Authors: Oliver NJ, Rabinovitch-Deere CA, Carroll AL, Nozzi NE, Case AE, Atsumi S Tags: Curr Opin Chem Biol Source Type: research

Enzymatic deconstruction of plant biomass by fungal enzymes.
Abstract Lignocellulosic plant biomass is the world's most abundant carbon source and has consequently attracted attention as a renewable resource for production of biofuels and commodity chemicals. Still the process is economically not fit enough to compete with then use of fossil resources, and the costs associated with enzymatic hydrolysis and product recovery are the major obstacle. The discovery of the role of non-hydrolytic enzymes in lignocellulose hydrolysis has recently contributed significant improvements to hydrolysis but also added new challenges to the biomass to ethanol process. Transfer of the new i...
Source: Current Opinion in Chemical Biology - September 7, 2016 Category: Biochemistry Authors: Kubicek CP, Kubicek EM Tags: Curr Opin Chem Biol Source Type: research

Central metabolic nodes for diverse biochemical production.
Abstract Central carbon metabolism is conserved among all organisms for cellular function and energy generation. The connectivity of this metabolic map gives rises to key metabolite nodes. Five of these nodes in particular, pyruvate, citric acid, tyrosine and aspartate, acetyl-CoA, serve as critical starting points for the generation of a broad class of relevant chemical molecules with ranging applications from fuels, pharmaceuticals and polymer precursors. This review highlights recent progress in converting these metabolite nodes into valuable products. In particular, acetyl-CoA, the most well-connected node, se...
Source: Current Opinion in Chemical Biology - September 5, 2016 Category: Biochemistry Authors: Cordova LT, Alper HS Tags: Curr Opin Chem Biol Source Type: research

Minimalist IR and fluorescence probes of protein function.
Abstract Spectroscopic studies of small proteins and peptides, especially those requiring fine spatial and/or temporal resolution, demand synthetic probes that confer the minimal possible steric and functional change on the native properties. Here we review the recent progress in development of minimally disruptive probes for fluorescence and infrared spectroscopies, as well as the methods to efficiently incorporate them into proteins. Advances in spectroscopy on the one hand result in high specialization of synthetic probes for a particular purpose, but on the other hand allow for the same probes be used for diff...
Source: Current Opinion in Chemical Biology - September 3, 2016 Category: Biochemistry Authors: Gosavi PM, Korendovych IV Tags: Curr Opin Chem Biol Source Type: research

Targeting biomolecules with reversible covalent chemistry.
Abstract Interaction of biomolecules typically proceeds in a highly selective and reversible manner, for which covalent bond formation has been largely avoided due to the potential difficulty of dissociation. However, employing reversible covalent warheads in drug design has given rise to covalent enzyme inhibitors that serve as powerful therapeutics, as well as molecular probes with exquisite target selectivity. This review article summarizes the recent advances in the development of reversible covalent chemistry for biological and medicinal applications. Specifically, we document the chemical strategies that all...
Source: Current Opinion in Chemical Biology - September 3, 2016 Category: Biochemistry Authors: Bandyopadhyay A, Gao J Tags: Curr Opin Chem Biol Source Type: research

Cameo appearances of aminoacyl-tRNA in natural product biosynthesis.
Abstract The breadth of unprecedented enzymatic reactions performed during the formation of microbial natural products has continued to expand as new biosynthetic gene clusters are unearthed by genome mining. Enzymes that use aminoacyl-tRNA (aa-tRNA) outside of the translation machinery have been known for decades, and accounts of their use in natural product biosynthesis are just beginning to accumulate. This review will highlight the recent discoveries and advances in our mechanistic understanding of aa-tRNA-dependent enzymes that play key roles in the biosynthesis of a growing number of microbial natural produc...
Source: Current Opinion in Chemical Biology - September 3, 2016 Category: Biochemistry Authors: Ulrich EC, van der Donk WA Tags: Curr Opin Chem Biol Source Type: research

Computational methods to design cyclic peptides.
Abstract Cyclic peptides (CPs) are promising modulators of protein-protein interactions (PPIs), but their application remains challenging. It is currently difficult to predict the structures and bioavailability of CPs. The ability to design CPs using computer modeling would greatly facilitate the development of CPs as potent PPI modulators for fundamental studies and as potential therapeutics. Herein, we describe computational methods to generate CP libraries for virtual screening, as well as current efforts to accurately predict the conformations adopted by CPs. These advances are making it possible to envision r...
Source: Current Opinion in Chemical Biology - September 1, 2016 Category: Biochemistry Authors: McHugh SM, Rogers JR, Solomon SA, Yu H, Lin YS Tags: Curr Opin Chem Biol Source Type: research

How PEGylation influences protein conformational stability.
Abstract PEGylation is an important strategy for enhancing the pharmacokinetic properties of protein therapeutics. The development of chemoselective side-chain modification reactions has enabled researchers to PEGylate proteins with high selectivity at defined locations. However, aside from avoiding active sites and binding interfaces, there are few guidelines for the selection of optimal PEGylation sites. Because conformational stability is intimately related to the ability of a protein to avoid proteolysis, aggregation, and immune responses, it is possible that PEGylating a protein at sites where PEG enhances co...
Source: Current Opinion in Chemical Biology - August 27, 2016 Category: Biochemistry Authors: Lawrence PB, Price JL Tags: Curr Opin Chem Biol Source Type: research

Enzymes for fatty acid-based hydrocarbon biosynthesis.
Abstract Surging energy consumption and environmental concerns have stimulated interest in the production of chemicals and fuels through sustainable and renewable approaches. Fatty acid-based hydrocarbons, such as alkanes and alkenes, are of particular interest to directly replace fossil fuels. Towards this effort, understanding of hydrocarbon-producing enzymes is the first indispensable step to bio-production of hydrocarbons. Here, we review recent advances in the discovery and mechanistic study of enzymes capable of converting fatty acid precursors into hydrocarbons, and provide perspectives on the future of thi...
Source: Current Opinion in Chemical Biology - August 26, 2016 Category: Biochemistry Authors: Herman NA, Zhang W Tags: Curr Opin Chem Biol Source Type: research

The expanding world of DNA and RNA.
Abstract DNA and RNA are remarkable because they can both encode information and possess desired properties, including the ability to bind specific targets or catalyze specific reactions. Nucleotide modifications that do not interfere with enzymatic synthesis are now being used to bestow DNA or RNA with properties that further increase their utility, including phosphate and sugar modifications that increase nuclease resistance, nucleobase modifications that increase the range of activities possible, and even whole nucleobase replacement that results in selective pairing and the creation of unnatural base pairs tha...
Source: Current Opinion in Chemical Biology - August 23, 2016 Category: Biochemistry Authors: Chen T, Hongdilokkul N, Liu Z, Thirunavukarasu D, Romesberg FE Tags: Curr Opin Chem Biol Source Type: research

Recent trends in metabolic engineering of microorganisms for the production of advanced biofuels.
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 isop...
Source: Current Opinion in Chemical Biology - August 20, 2016 Category: Biochemistry Authors: Cheon S, Kim HM, Gustavsson M, Lee SY Tags: Curr Opin Chem Biol Source Type: research

The formate bio-economy.
Abstract In this review we discuss the concept of the formate bio-economy: formate can be produced efficiently from various available resources and can be consumed by microbes as the sole carbon source for the production of value-added chemicals, directly addressing major challenges in energy storage and chemical production. We show that the formate assimilation pathways utilized by natural formatotrophs are either inefficient or are constrained to organisms that are difficult to cultivate and engineer. Instead, adapting model industrial organisms to formatotrophic growth using synthetic, specially tailored format...
Source: Current Opinion in Chemical Biology - July 23, 2016 Category: Biochemistry Authors: Yishai O, Lindner SN, Gonzalez de la Cruz J, Tenenboim H, Bar-Even A Tags: Curr Opin Chem Biol Source Type: research

Chemical genetics approaches for selective intervention in epigenetics.
Abstract Chemical genetics is the use of biologically active small molecules (chemical probes) to investigate the functions of gene products, through the modulation of protein activity. Recent years have seen significant progress in the application of chemical genetics to study epigenetics, following the development of new chemical probes, a growing appreciation of the role of epigenetics in disease and a recognition of the need and utility of high-quality, cell-active chemical probes. In this review, we single out the bromodomain reader domains as a prime example of both the success, and challenges facing chemica...
Source: Current Opinion in Chemical Biology - July 13, 2016 Category: Biochemistry Authors: Runcie AC, Chan KH, Zengerle M, Ciulli A Tags: Curr Opin Chem Biol Source Type: research

Biochemical and synthetic biology approaches to improve photosynthetic CO2-fixation.
Abstract There is an urgent need to improve agricultural productivity to secure future food and biofuel supply. Here, we summarize current approaches that aim at improving photosynthetic CO2-fixation. We critically review, compare and comment on the four major lines of research towards this aim, which focus on (i) improving RubisCO, the CO2-fixing enzyme in photosynthesis, (ii) implementing CO2-concentrating mechanisms, (iii) establishing synthetic photorespiration bypasses, and (iv) engineering synthetic CO2-fixation pathways. PMID: 27400232 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - July 8, 2016 Category: Biochemistry Authors: Erb TJ, Zarzycki J Tags: Curr Opin Chem Biol Source Type: research

Molecular imaging with CARS micro-spectroscopy.
Abstract After more than a decade of instrument and method development, broadband coherent anti-Stokes Raman scattering (CARS) micro-spectroscopy is beginning to live up to its potential as a label-free imaging modality that can rapidly generate high resolution images with full vibrational spectra at each image pixel. Presently these instruments are able to obtain quantitative, spatially resolved information on lipids from the CH stretch region of the Raman spectrum, and some instrument designs facilitate acquisition of high quality fingerprint spectra, containing information on a host of molecular species includi...
Source: Current Opinion in Chemical Biology - July 8, 2016 Category: Biochemistry Authors: Cicerone M Tags: Curr Opin Chem Biol Source Type: research

iPAD or PADi-'tablets' with therapeutic disease potential?
Abstract Over the last five years, a growing body of literature has strengthened the rationale for the involvement of PAD (protein arginine deiminase) enzymes in diverse diseases, through direct roles of citrullination in mechanisms such as neutrophil extracellular trap formation and immune complex formation. The recent development of inhibitors of the PAD family, coupled with the availability of mice genetically deficient in PAD2 or PAD4, has accelerated understanding of the role of these targets in varied disease models. This review surveys the recent literature to confirm the therapeutic potential of PAD inhibi...
Source: Current Opinion in Chemical Biology - June 30, 2016 Category: Biochemistry Authors: Lewis HD, Nacht M Tags: Curr Opin Chem Biol Source Type: research

Go in! Go out! Inducible control of nuclear localization.
Abstract Cells have evolved a variety of mechanisms to regulate the enormous complexity of processes taking place inside them. One mechanism consists in tightly controlling the localization of macromolecules, keeping them away from their place of action until needed. Since a large fraction of the cellular response to external stimuli is mediated by gene expression, it is not surprising that transcriptional regulators are often subject to stimulus-induced nuclear import or export. Here we review recent methods in chemical biology and optogenetics for controlling the nuclear localization of proteins of interest insi...
Source: Current Opinion in Chemical Biology - June 30, 2016 Category: Biochemistry Authors: Di Ventura B, Kuhlman B Tags: Curr Opin Chem Biol Source Type: research

Epiproteomics: quantitative analysis of histone marks and codes by mass spectrometry.
Abstract Histones are a group of proteins with a high number of post-translational modifications, including methylation, acetylation, phosphorylation, and monoubiquitination, which play critical roles in every chromatin-templated activity. The quantitative analysis of these modifications using mass spectrometry (MS) has seen significant improvements over the last decade. It is now possible to perform large-scale surveys of dozens of histone marks and hundreds of their combinations on global chromatin. Here, we review the development of three MS strategies for analyzing histone modifications that have come to be kn...
Source: Current Opinion in Chemical Biology - June 29, 2016 Category: Biochemistry Authors: Zheng Y, Huang X, Kelleher NL Tags: Curr Opin Chem Biol Source Type: research

Advances and challenges in understanding histone demethylase biology.
Abstract Within the last decade we have witnessed significant progress in the field of chromatin methylation, ranging from the discovery that chromatin methylation is reversible, to the identification of two classes of oxidative chromatin demethylases. Multiple genetic and cellular studies emphasize the role of members of the amine oxidase and 2-oxoglutarate oxygenase enzyme families involved in methyl-lysine in physiology and disease. Advances in understanding of the underlying biochemistry have resulted in development of first series of clinical inhibitors and tool compounds which continue to resolve and help un...
Source: Current Opinion in Chemical Biology - June 29, 2016 Category: Biochemistry Authors: Nowak RP, Tumber A, Johansson C, Che KH, Brennan P, Owen D, Oppermann U Tags: Curr Opin Chem Biol Source Type: research

Histone deacetylase 3 (HDAC 3) as emerging drug target in NF-κB-mediated inflammation.
Histone deacetylase 3 (HDAC 3) as emerging drug target in NF-κB-mediated inflammation. Curr Opin Chem Biol. 2016 Jun 29;33:160-168 Authors: Leus NG, Zwinderman MR, Dekker FJ Abstract Activation of inflammatory gene expression is regulated, among other factors, by post-translational modifications of histone proteins. The most investigated type of histone modifications is lysine acetylations. Histone deacetylases (HDACs) remove acetylations from lysines, thereby influencing (inflammatory) gene expression. Intriguingly, apart from histones, HDACs also target non-histone proteins. The nuclear factor...
Source: Current Opinion in Chemical Biology - June 29, 2016 Category: Biochemistry Authors: Leus NG, Zwinderman MR, Dekker FJ Tags: Curr Opin Chem Biol Source Type: research

Rethinking translational nanomedicine: insights from the 'bottom-up' design of the Porphysome for guiding the clinical development of imageable nanomaterials.
Abstract Progress in therapeutics and biotechnologies leveraging new insights in our understanding of cancer biology and progression have had an underwhelming clinical significance thus far. A key challenge arising from the creation of nanomedicines consolidating multiple desirable functionalities into a 'all-in-one' platform is that the layering of functionalities into a single agent introduces novel complexities that significantly impede clinical translation. An alternative design approach seeks to exploit intrinsically multi-functional building block to assemble nanomedicines from the bottom-up, yielding agents...
Source: Current Opinion in Chemical Biology - June 25, 2016 Category: Biochemistry Authors: Valic MS, Zheng G Tags: Curr Opin Chem Biol Source Type: research

Communicating artificial cells.
sy SS Abstract Intercellular chemical communication is commonly exploited for the engineering of living cells but has been largely ignored by efforts to build artificial cells. Since communication is a fundamental feature of life, the construction of artificial cells capable of chemical communication will likely lead to a deeper understanding of biology and allow for the development of life-like technologies. Herein we highlight recent progress towards the construction of artificial systems that are capable of chemically communicating with natural living cells. Artificial systems that exploit both biological and a...
Source: Current Opinion in Chemical Biology - June 25, 2016 Category: Biochemistry Authors: Lentini R, Yeh Martín N, Mansy SS Tags: Curr Opin Chem Biol Source Type: research

Pseudouridine: the fifth RNA nucleotide with renewed interests.
Abstract More than 100 different types of chemical modifications to RNA have been documented so far. Historically, most of these modifications were found in rRNA, tRNA and snRNA; recently, new methods aided by high-throughput sequencing have enabled identification of chemical modifications to mRNA, leading to the emerging field of 'RNA epigenetics'. One such example is pseudouridine, which has long been known as a RNA modification in abundant non-coding RNA (ncRNA) and has recently been found to be present in mRNAas well. This review first summarizes biogenesis and known functions of pseudouridine in ncRNAs. We th...
Source: Current Opinion in Chemical Biology - June 24, 2016 Category: Biochemistry Authors: Li X, Ma S, Yi C Tags: Curr Opin Chem Biol Source Type: research

Harnessing cyanine photooxidation: from slowing photobleaching to near-IR uncaging.
Abstract Light provides a uniquely powerful stimulus to help visualize and/or perturb biological systems. The use of tissue penetrant near-IR wavelengths enables in vivo applications, however the design of molecules that function in this range remains a substantial challenge. Heptamethine cyanine fluorophores are already important tools for near-IR optical imaging. These molecules are susceptible to photobleaching through a photooxidative cleavage reaction. This review details efforts to define the mechanism of this reaction and two emerging fields closely tied to this process. In the first, efforts that slow phot...
Source: Current Opinion in Chemical Biology - June 24, 2016 Category: Biochemistry Authors: Gorka AP, Schnermann MJ Tags: Curr Opin Chem Biol Source Type: research

Chemical probes for methyl lysine reader domains.
Abstract The primary intent of a chemical probe is to establish the relationship between a molecular target, usually a protein whose function is modulated by the probe, and the biological consequences of that modulation. In order to fulfill this purpose, a chemical probe must be profiled for selectivity, mechanism of action, and cellular activity, as the cell is the minimal system in which 'biology' can be explored. This review provides a brief overview of progress towards chemical probes for methyl lysine reader domains with a focus on recent progress targeting chromodomains. PMID: 27348158 [PubMed - as supp...
Source: Current Opinion in Chemical Biology - June 24, 2016 Category: Biochemistry Authors: James LI, Frye SV Tags: Curr Opin Chem Biol Source Type: research

Ribosome-mediated synthesis of natural product-like peptides via cell-free translation.
Abstract Peptide natural products (PNPs) represent a unique class of compounds known for their fascinating structural motifs with important biological activities. Lately, PNPs have garnered a lot of interest for their application in drug discovery. Nevertheless, lack of diversity oriented synthetic/biosynthetic platforms to generate large natural product-like libraries has limited their development as peptide therapeutics. The promiscuity of cell-free translation has allowed for the synthesis of artificial PNPs having complex structural features. Modified cell-free translation systems coupled with the display tech...
Source: Current Opinion in Chemical Biology - June 23, 2016 Category: Biochemistry Authors: Maini R, Umemoto S, Suga H Tags: Curr Opin Chem Biol Source Type: research