Preclinical characterization and clinical development of ILARIS(®) (canakinumab) for the treatment of autoinflammatory diseases.
Preclinical characterization and clinical development of ILARIS(®) (canakinumab) for the treatment of autoinflammatory diseases. Curr Opin Chem Biol. 2015 Dec 22;32:1-9 Authors: Gram H Abstract Interleukin-1beta (IL-1β) is a pro-inflammatory cytokine which is part of the first line innate response in vertebrates and is induced in injury, infection, and immunity. While temporally limited induction of IL-1β is believed to protect the organisms against traumatic or infectious insults, its aberrant expression in chronic inflammation is detrimental. Therefore, pharmacological neutralization o...
Source: Current Opinion in Chemical Biology - December 22, 2015 Category: Biochemistry Authors: Gram H Tags: Curr Opin Chem Biol Source Type: research

Combinatorial biosynthesis of RiPPs: docking with marine life.
Abstract Ribosomally synthesized natural products are found in all forms of life. Their biosynthesis uses simple ribosomally synthesized peptides as starting materials that are transformed into complex structures via posttranslational modifications, enriched with elaborate chemical scaffolds that make them desirable as pharmacological tools. In addition, these natural products often exhibit combinatorial biosynthesis, making them attractive targets for engineering. An increasing knowledge of their biosynthetic machinery has provided key insights into their fascinating chemistry. Marine organisms have been a rich s...
Source: Current Opinion in Chemical Biology - December 19, 2015 Category: Biochemistry Authors: Sardar D, Schmidt EW Tags: Curr Opin Chem Biol Source Type: research

A roadmap for the XCMS family of software solutions in metabolomics.
The objective of this review is to provide an overview of the freely available bioinformatic solutions that are either based upon or are compatible with the algorithms in XCMS, which we broadly refer to here as the 'XCMS family' of software. These include CAMERA, credentialing, Warpgroup, metaXCMS, X(13)CMS, and XCMS Online. Together, these informatic technologies can accommodate most cutting-edge metabolomic applications and offer unique advantages when compared to the original XCMS program. PMID: 26673825 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - December 10, 2015 Category: Biochemistry Authors: Mahieu NG, Genenbacher JL, Patti GJ Tags: Curr Opin Chem Biol Source Type: research

Proteomic analysis of fatty-acylated proteins.
Abstract Protein fatty-acylation in eukaryotes has been associated with many fundamental biological processes. However, the diversity, abundance and regulatory mechanisms of protein fatty-acylation in vivo remain to be explored. Herein, we review the proteomic analysis of fatty-acylated proteins, with a focus on N-myristoylation and S-palmitoylation. We then highlight major challenges and emerging methods for direct site identification, quantitation, and lipid structure characterization to understand the functions and regulatory mechanisms of fatty-acylated proteins in physiology and disease. PMID: 26656971 [...
Source: Current Opinion in Chemical Biology - December 2, 2015 Category: Biochemistry Authors: Peng T, Thinon E, Hang HC Tags: Curr Opin Chem Biol Source Type: research

Mapping proteome-wide interactions of reactive chemicals using chemoproteomic platforms.
Abstract A large number of pharmaceuticals, endogenous metabolites, and environmental chemicals act through covalent mechanisms with protein targets. Yet, their specific interactions with the proteome still remain poorly defined for most of these reactive chemicals. Deciphering direct protein targets of reactive small-molecules is critical in understanding their biological action, off-target effects, potential toxicological liabilities, and development of safer and more selective agents. Chemoproteomic technologies have arisen as a powerful strategy that enable the assessment of proteome-wide interactions of these...
Source: Current Opinion in Chemical Biology - November 28, 2015 Category: Biochemistry Authors: Counihan JL, Ford B, Nomura DK Tags: Curr Opin Chem Biol Source Type: research

Metabolic control of methylation and acetylation.
Abstract Methylation and acetylation of DNA and histone proteins are the chemical basis for epigenetics. From bacteria to humans, methylation and acetylation are sensitive to cellular metabolic status. Modification rates depend on the availability of one-carbon and two-carbon substrates (S-adenosylmethionine, acetyl-CoA, and in bacteria also acetyl-phosphate). In addition, they are sensitive to demodification enzyme cofactors (α-ketoglutarate, NAD(+)) and structural analog metabolites that function as epigenetic enzyme inhibitors (e.g., S-adenosylhomocysteine, 2-hydroxyglutarate). Methylation and acetylation...
Source: Current Opinion in Chemical Biology - November 26, 2015 Category: Biochemistry Authors: Su X, Wellen KE, Rabinowitz JD Tags: Curr Opin Chem Biol Source Type: research

Covalent targeting of acquired cysteines in cancer.
Abstract The thiolate side chain of cysteine has a unique functionality that drug hunters and chemical biologists have begun to exploit. For example, targeting cysteine residues in the ATP-binding pockets of kinases with thiol-reactive molecules has afforded increased selectivity and potency to drugs like imbrutinib, which inhibits the oncogene BTK, and CO-1686 and AZD9291 that target oncogenic mutant EGFR. Recently, disulfide libraries and targeted GDP-mimetics have been used to selectively label the G12C oncogenic mutation in KRAS. We reasoned that other oncogenes contain mutations to cysteine, and thus screened...
Source: Current Opinion in Chemical Biology - November 26, 2015 Category: Biochemistry Authors: Visscher M, Arkin MR, Dansen TB Tags: Curr Opin Chem Biol Source Type: research

Chemoproteomic profiling of protein modifications by lipid-derived electrophiles.
Abstract Lipid-derived electrophiles (LDEs) are a group of endogenous reactive metabolites generated as products of lipid peroxidation when cells are under oxidative stress. LDEs are able to covalently modify nucleophilic residues in proteins to alter their structures and activities, either resulting in irreversible functional damage or triggering aberrant signaling pathways. Traditional biochemical methods have revealed individual protein targets modified by LDEs, however, deciphering the toxicity and/or signaling roles of LDEs requires systematic studies of these modifications in a high-throughput fashion. Here ...
Source: Current Opinion in Chemical Biology - November 25, 2015 Category: Biochemistry Authors: Chen Y, Qin W, Wang C Tags: Curr Opin Chem Biol Source Type: research

RNA epigenetics-chemical messages for posttranscriptional gene regulation.
Abstract Chemical modifications in cellular RNA are diverse and abundant. Commonly found in ribosomal RNA (rRNA), transfer RNA (tRNA), long-noncoding RNA (lncRNA), and small nuclear (snRNA), these components play various structural and functional roles. Until recently, the roles of chemical modifications within messenger RNA (mRNA) have been understudied. Recent maps of several mRNA modifications have suggested regulatory functions for these marks. This review summarizes recent advances in identifying and understanding biological roles of posttranscriptional mRNA modification, or 'RNA epigenetics', with an emphasi...
Source: Current Opinion in Chemical Biology - November 25, 2015 Category: Biochemistry Authors: Roundtree IA, He C Tags: Curr Opin Chem Biol Source Type: research

Polytheonamide biosynthesis showcasing the metabolic potential of sponge-associated uncultivated 'Entotheonella' bacteria.
Abstract The vast majority of microorganisms on the planet have not been grown under laboratory conditions due to unknown metabolic and environmental constraints. This uncultivated majority has enormous potential as a reservoir of unique enzymology and biosynthetic pathways. The following review offers a glimpse into this unexplored enzymatic stockpile through recent progress made on the biosynthesis of the potent polytheonamide cytotoxins. These structurally highly complex pore-forming peptides, isolated from the marine sponge Theonella swinhoei, are synthesized by the ribosome and then modified through numerous ...
Source: Current Opinion in Chemical Biology - November 25, 2015 Category: Biochemistry Authors: Freeman MF, Vagstad AL, Piel J Tags: Curr Opin Chem Biol Source Type: research

Advances in discovering small molecules to probe protein function in a systems context.
Abstract High throughput screening (HTS) has historically been used for drug discovery almost exclusively by the pharmaceutical industry. Due to a significant decrease in costs associated with establishing a high throughput facility and an exponential interest in discovering probes of development and disease associated biomolecules, HTS core facilities have become an integral part of most academic and non-profit research institutions over the past decade. This major shift has led to the development of new HTS methodologies extending beyond the capabilities and target classes used in classical drug discovery approa...
Source: Current Opinion in Chemical Biology - November 23, 2015 Category: Biochemistry Authors: Doyle SK, Pop MS, Evans HL, Koehler AN Tags: Curr Opin Chem Biol Source Type: research

Unusual chemistries in fungal meroterpenoid biosynthesis.
Abstract Meroterpenoids are polyketide and terpenoid hybrid natural products with remarkable biological activities. Recent progress in fungal meroterpenoid biosynthesis has revealed several unusual enzyme reactions and novel enzymes, including unique terpene cyclization reactions by a novel family of membrane-bound terpene cyclases and post-cyclization modification reactions by oxygenases, such as non-heme iron-dependent dioxygenases, flavin adenine dinucleotide-dependent monooxygenases, and cytochrome P450 monooxygenases. They contribute to the structural diversification and increase in complexity of fungal merot...
Source: Current Opinion in Chemical Biology - November 20, 2015 Category: Biochemistry Authors: Matsuda Y, Awakawa T, Mori T, Abe I Tags: Curr Opin Chem Biol Source Type: research

Mechanisms of mechanosensing-mechanosensitive channels, function and re-engineering.
Abstract Sensing and responding to mechanical stimuli is an ancient behavior and ubiquitous to all forms of life. One of its players 'mechanosensitive ion channels' are involved in processes from osmosensing in bacteria to pain in humans. However, the mechanism of mechanosensing is yet to be elucidated. This review describes recent developments in the understanding of a bacterial mechanosensitive channel. Force from the lipid principle of mechanosensation, new methods to understand protein-lipid interactions, the role of water in the gating, the use of engineered mechanosensitive channels in the understanding of t...
Source: Current Opinion in Chemical Biology - November 20, 2015 Category: Biochemistry Authors: Kocer A Tags: Curr Opin Chem Biol Source Type: research

Applications in high-content functional protein microarrays.
Abstract Protein microarray technology provides a versatile platform for characterization of hundreds to thousands of proteins in a parallel and high-throughput manner. Over the last decade, applications of functional protein microarrays in particular have flourished in studying protein function at a systems level and have led to the construction of networks and pathways describing these functions. Relevant areas of research include the detection of various binding properties of proteins, the study of enzyme-substrate relationships, the analysis of host-microbe interactions, and profiling antibody specificity. In ...
Source: Current Opinion in Chemical Biology - November 18, 2015 Category: Biochemistry Authors: Moore CD, Ajala OZ, Zhu H Tags: Curr Opin Chem Biol Source Type: research

Editorial overview: Mechanistic biology: Dynamic interactions in biology-sensing change.
PMID: 26598929 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - November 17, 2015 Category: Biochemistry Authors: Booth PJ, Regan L Tags: Curr Opin Chem Biol Source Type: research

Reconciling proteomics with next generation sequencing.
Abstract Both genomics and proteomics technologies have matured in the last decade to a level where they are able to deliver system-wide data on the qualitative and quantitative abundance of their respective molecular entities, that is DNA/RNA and proteins. A next logical step is the collective use of these technologies, ideally gathering data on matching samples. The first large scale so-called proteogenomics studies are emerging, and display the benefits each of these layers of analysis has on the other layers to together generate more meaningful insight into the connection between the phenotype/physiology and g...
Source: Current Opinion in Chemical Biology - November 16, 2015 Category: Biochemistry Authors: Low TY, Heck AJ Tags: Curr Opin Chem Biol Source Type: research

Lignocellulose degradation mechanisms across the Tree of Life.
Abstract Organisms use diverse mechanisms involving multiple complementary enzymes, particularly glycoside hydrolases (GHs), to deconstruct lignocellulose. Lytic polysaccharide monooxygenases (LPMOs) produced by bacteria and fungi facilitate deconstruction as does the Fenton chemistry of brown-rot fungi. Lignin depolymerisation is achieved by white-rot fungi and certain bacteria, using peroxidases and laccases. Meta-omics is now revealing the complexity of prokaryotic degradative activity in lignocellulose-rich environments. Protists from termite guts and some oomycetes produce multiple lignocellulolytic enzymes. ...
Source: Current Opinion in Chemical Biology - November 13, 2015 Category: Biochemistry Authors: Cragg SM, Beckham GT, Bruce NC, Bugg TD, Distel DL, Dupree P, Etxabe AG, Goodell BS, Jellison J, McGeehan JE, McQueen-Mason SJ, Schnorr K, Walton PH, Watts JE, Zimmer M Tags: Curr Opin Chem Biol Source Type: research

Editorial overview: Energy: Prospects for fuels and chemicals from a biomass-based biorefinery using post-genomic chemical biology tools.
PMID: 26574194 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - November 10, 2015 Category: Biochemistry Authors: Bugg TD, Resch MG Tags: Curr Opin Chem Biol Source Type: research

High-throughput platforms for metabolomics.
Abstract Mass spectrometry has become a choice method for broad-spectrum metabolite analysis in both fundamental and applied research. This can range from comprehensive analysis achieved through time-consuming chromatography to the rapid analysis of a few target metabolites without chromatography. In this review article, we highlight current high-throughput MS-based platforms and their potential application in metabolomics. Although current MS platforms can reach throughputs up to 0.5seconds per sample, the metabolite coverage of these platforms are low compared to low-throughput, separation-based MS methods. High...
Source: Current Opinion in Chemical Biology - November 3, 2015 Category: Biochemistry Authors: de Raad M, Fischer CR, Northen TR Tags: Curr Opin Chem Biol Source Type: research

Mechanisms employed by cellulase systems to gain access through the complex architecture of lignocellulosic substrates.
Abstract To improve the deconstruction of biomass, the most abundant terrestrial source of carbon polymers, en route to renewable fuels, chemicals, and materials more knowledge is needed into the mechanistic interplay between thermochemical pretreatment and enzymatic hydrolysis. In this review we highlight recent progress in advanced imaging techniques that have been used to elucidate the effects of thermochemical pretreatment on plant cell walls across a range of spatial scales and the relationship between the substrate structure and the function of various glycoside hydrolase components. The details of substrate...
Source: Current Opinion in Chemical Biology - October 31, 2015 Category: Biochemistry Authors: Donohoe BS, Resch MG Tags: Curr Opin Chem Biol Source Type: research

Dynamics of co-translational protein targeting.
Abstract Most membrane and secretory proteins are delivered co-translationally to protein translocation channels in their destination membrane by the signal recognition particle (SRP) and its receptor. This co-translational molecular machinery is conserved across all kingdoms of life, though it varies in composition and function. Here we report recent progress towards understanding the mechanism of SRP function, focusing on findings about Escherichia coli SRP's conformational dynamics throughout the targeting process. These insights shed light on a key checkpoint in the targeting cycle: how SRP regulates engagemen...
Source: Current Opinion in Chemical Biology - October 27, 2015 Category: Biochemistry Authors: Elvekrog MM, Walter P Tags: Curr Opin Chem Biol Source Type: research

Mechanobiology-chemical origin of membrane mechanical resistance and force-dependent signaling.
Abstract The cell membrane is a highly complex designed material with remarkable physicochemical properties; comprised mainly of lipid moieties, it is capable of self-assembling, changing morphology, housing a range of distinct proteins, and withstanding electrical, chemical and mechanical perturbations. All of these fundamental cellular functions occurring within a 5nm thick film is an astonishing feat of engineering, made possible due to the interplay of a variety of intermolecular forces. Elucidating how the interactions within the chemically distinct partners influence the nanomechanical properties of the memb...
Source: Current Opinion in Chemical Biology - October 27, 2015 Category: Biochemistry Authors: Beedle AE, Williams A, Relat-Goberna J, Garcia-Manyes S Tags: Curr Opin Chem Biol Source Type: research

Secrets of a covalent interaction for biomaterials and biotechnology: SpyTag and SpyCatcher.
Abstract SpyTag is a short peptide that forms an isopeptide bond upon encountering its protein partner SpyCatcher. This covalent peptide interaction is a simple and powerful tool for bioconjugation and extending what protein architectures are accessible. Here we review the origin and mechanism of SpyTag/SpyCatcher, focusing on recent innovative applications. Ligation of targeting-antibody with antigen provided a simple route to vaccine generation. SpyRings, from head-to-tail cyclisation, gave major enhancements in enzyme resilience. Linking multiple SpyCatchers gave dendrimers for T-cell activation or Spy networks...
Source: Current Opinion in Chemical Biology - October 27, 2015 Category: Biochemistry Authors: Reddington SC, Howarth M Tags: Curr Opin Chem Biol Source Type: research

Detection and identification of protein citrullination in complex biological systems.
Abstract Protein citrullination is a post-translational modification of arginine that is catalyzed by the Protein Arginine Deiminase (PAD) family of enzymes. Aberrantly increased citrullination is associated with a host of inflammatory diseases and cancer and PAD inhibitors have shown remarkable efficacy in a range of diseases including rheumatoid arthritis, lupus, atherosclerosis, and ulcerative colitis. In rheumatoid arthritis, citrullinated proteins serve as key antigens for rheumatoid arthritis-associated autoantibodies. These data suggest that citrullinated proteins may serve more generally as biomarkers of s...
Source: Current Opinion in Chemical Biology - October 27, 2015 Category: Biochemistry Authors: Clancy KW, Weerapana E, Thompson PR Tags: Curr Opin Chem Biol Source Type: research

How specific is CRISPR/Cas9 really?
Abstract The specificity of RNA-guided nucleases has gathered considerable interest as they become broadly applied to basic research and therapeutic development. Reports of the simple generation of animal models and genome engineering of cells raised questions about targeting precision. Conflicting early reports led the field to believe that CRISPR/Cas9 system was promiscuous, leading to a variety of strategies for improving specificity and increasingly sensitive methods to detect off-target events. However, other studies have suggested that CRISPR/Cas9 is a highly specific genome-editing tool. This review will fo...
Source: Current Opinion in Chemical Biology - October 23, 2015 Category: Biochemistry Authors: O'Geen H, Yu AS, Segal DJ Tags: Curr Opin Chem Biol Source Type: research

Three steps forward, two steps back: mechanistic insights into the assembly and disassembly of the SNARE complex.
Abstract Membrane fusion is a tightly controlled process in all eukaryotic cell types. The SNARE family of proteins is required for fusion throughout the exocytic and endocytic trafficking pathways. SNAREs on a transport vesicle interact with the cognate SNAREs on the target membrane, forming an incredibly stable SNARE complex that provides energy for the membranes to fuse, although many aspects of the mechanism remain elusive. Recent advances in single-molecule and high-resolution structural methods provide exciting new insights into how SNARE complexes assemble, including measurements of assembly energetics and ...
Source: Current Opinion in Chemical Biology - October 22, 2015 Category: Biochemistry Authors: Bombardier JP, Munson M Tags: Curr Opin Chem Biol Source Type: research

Synthetic biology for microbial production of lipid-based biofuels.
Abstract The risks of maintaining current CO2 emission trends have led to interest in producing biofuels using engineered microbes. Microbial biofuels reduce emissions because CO2 produced by fuel combustion is offset by CO2 captured by growing biomass, which is later used as feedstock for biofuel fermentation. Hydrocarbons found in petroleum fuels share striking similarity with biological lipids. Here we review synthetic metabolic pathways based on fatty acid and isoprenoid metabolism to produce alkanes and other molecules suitable as biofuels. We further discuss engineering strategies to optimize engineered bios...
Source: Current Opinion in Chemical Biology - October 16, 2015 Category: Biochemistry Authors: d'Espaux L, Mendez-Perez D, Li R, Keasling JD Tags: Curr Opin Chem Biol Source Type: research

Editorial overview: Opportunities and challenges in synthetic biology.
PMID: 26456417 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - October 8, 2015 Category: Biochemistry Authors: Chang MC, Zhao H Tags: Curr Opin Chem Biol Source Type: research

Chemically induced dimerization: reversible and spatiotemporal control of protein function in cells.
u YW Abstract Small-molecule perturbation of biological systems is able to tackle biological problems that are not accessible by classical genetic interference methods. Chemically induced dimerization (CID) has been used as a valuable tool to study various biological processes. Recent years have seen tremendous progress in the development of orthogonal and reversible CID systems. These new systems allow control over protein function with unprecedented precision and spatiotemporal resolution. While the primary application of CID has been on dissecting signal transductions, new emerging approaches have extended the ...
Source: Current Opinion in Chemical Biology - September 29, 2015 Category: Biochemistry Authors: Voß S, Klewer L, Wu YW Tags: Curr Opin Chem Biol Source Type: research

Combining C6 and C5 sugar metabolism for enhancing microbial bioconversion.
Abstract Mixed sugars, which are often obtained from renewable biomass, can be converted into biofuels and chemicals by microbial conversion. This sustainable production process can also mitigate man-made climate change when used to petroleum-based fuel and chemical production. In contrast to single sugar fermentations, such as corn-based or sugarcane-based ethanol fermentations, mixed sugar fermentations present significant challenges for cost-effective production of the target products. In particular, inefficient and slow microbial fermentation of non-glucose sugars, such as galactose and xylose from the depolym...
Source: Current Opinion in Chemical Biology - September 29, 2015 Category: Biochemistry Authors: Zhang GC, Liu JJ, Kong II, Kwak S, Jin YS Tags: Curr Opin Chem Biol Source Type: research

Editorial overview: Synthetic biomolecules: Synthetic protein modifications-a giant leap towards understanding and generating biological functions.
PMID: 26403808 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - September 21, 2015 Category: Biochemistry Authors: Hackenberger CP, Chen PR Tags: Curr Opin Chem Biol Source Type: research

Alkane production from biomass: chemo-, bio- and integrated catalytic approaches.
BF Abstract Linear, branched and cyclic alkanes are important intermediates and end products of the chemical industry and are nowadays mainly obtained from fossil resources. In search for alternatives, biomass feedstocks are often presented as a renewable carbon source for the production of fuels, chemicals and materials. However, providing a complete market for all these applications seems unrealistic due to both financial and logistic issues. Despite the very large scale of current alkane-based fuel applications, biomass definitely has the potential to offer a partial solution to the fuel business. For the smal...
Source: Current Opinion in Chemical Biology - September 8, 2015 Category: Biochemistry Authors: Deneyer A, Renders T, Van Aelst J, Van den Bosch S, Gabriëls D, Sels BF Tags: Curr Opin Chem Biol Source Type: research

Protein-polymer conjugation-moving beyond PEGylation.
Abstract In this review, we summarize-from a materials science perspective-the current state of the field of polymer conjugates of peptide and protein drugs, with a focus on polymers that have been developed as alternatives to the current gold standard, poly(ethylene glycol) (PEG). PEGylation, or the covalent conjugation of PEG to biological therapeutics to improve their therapeutic efficacy by increasing their circulation half-lives and stability, has been the gold standard in the pharmaceutical industry for several decades. After years of research and development, the limitations of PEG, specifically its non-deg...
Source: Current Opinion in Chemical Biology - September 7, 2015 Category: Biochemistry Authors: Qi Y, Chilkoti A Tags: Curr Opin Chem Biol Source Type: research

Genetic manipulation of lignocellulosic biomass for bioenergy.
Abstract Lignocellulosic biomass represents an abundant and sustainable raw material for biofuel production. The recalcitrance of biomass to degradation increases the estimated cost of biofuel production and limits its competitiveness in the market. Genetic engineering of lignin, a major recalcitrance factor, improves saccharification and thus the potential yield of biofuels. Recently, our understanding of lignification and its regulation has been advanced by new studies in various systems, all of which further enhances our ability to manipulate the biosynthesis and deposition of lignin in energy crops for produci...
Source: Current Opinion in Chemical Biology - September 3, 2015 Category: Biochemistry Authors: Wang P, Dudareva N, Morgan JA, Chapple C Tags: Curr Opin Chem Biol Source Type: research

An emerging playbook for antibody-drug conjugates: lessons from the laboratory and clinic suggest a strategy for improving efficacy and safety.
Abstract Antibody-drug conjugates (ADCs) have become de rigueur for pharmaceutical oncology drug development pipelines. There are more than 40 ADCs undergoing clinical trials and many more in preclinical development. The field has rushed to follow the initial successes of Kadcyla™ and Adcetris™, and moved forward with new targets without much pause for optimization. In some respects, the ADC space has become divided into the clinical realm-where the proven technologies continue to represent the bulk of clinical candidates with a few exceptions-and the research realm-where innovations in conjugation che...
Source: Current Opinion in Chemical Biology - August 21, 2015 Category: Biochemistry Authors: Drake PM, Rabuka D Tags: Curr Opin Chem Biol Source Type: research

Genetic code expansion enabled site-specific dual-color protein labeling: superresolution microscopy and beyond.
Abstract Genetic code expansion is emerging as an important tool for manipulation and labeling of proteins in vitro and in vivo. In combination with click-chemistry it allows site-specific labeling of target proteins with small organic fluorophores. This is achieved by cotranslational incorporation of noncanonical amino acids (ncAAs) in target proteins via orthogonal tRNA/amino-acyl tRNA synthetase pairs. In a subsequent step, ncAAs are labeled with small dyes via click-chemistry. Small labeling tags and free choice of which fluorophore to use and where to put it into the protein are of particular importance for s...
Source: Current Opinion in Chemical Biology - August 21, 2015 Category: Biochemistry Authors: Nikić I, Lemke EA Tags: Curr Opin Chem Biol Source Type: research

The emergence of commodity-scale genetic manipulation.
Abstract Since the 1970s technological advancements in the fields of synthetic biology and metabolic engineering have led to a dramatic reduction in both time and cost required for generating genomic mutations in a variety of organisms. The union of genomic editing machinery, DNA inkjet printers, and bioinformatics algorithms allows engineers to design a library of thousands of unique oligos as well as build and test these designs on a ∼2 months time-scale and at a cost of roughly ∼0.3 cents per base pair. The implications of these capabilities for a variety of fields are far-reaching, with potential impac...
Source: Current Opinion in Chemical Biology - August 18, 2015 Category: Biochemistry Authors: Halweg-Edwards AL, Grau WC, Winkler JD, Garst AD, Gill RT Tags: Curr Opin Chem Biol Source Type: research

Protein-specific imaging of posttranslational modifications.
Abstract Protein posttranslational modifications (PTMs) modulate protein function, trafficking, and interactions. Many PTMs ubiquitously occurs on hundreds and thousands of proteins, which makes cellular imaging of the PTM state of a specific protein like looking for a needle in a haystack. A proximity-enabled strategy, which exploits the spatial proximity between the PTM and the modified protein, has emerged as a valuable tool for protein-specific imaging of PTMs in single cells and tissue sections. The protein and the PTM are dually labeled with two distinct tags, which enable the generation of the nanometer pro...
Source: Current Opinion in Chemical Biology - August 17, 2015 Category: Biochemistry Authors: Lin W, Gao L, Chen X Tags: Curr Opin Chem Biol Source Type: research

Orthogonal bioorthogonal chemistries.
This article highlights the development of orthogonal bioorthogonal reactions and their application in multi-target imaging and macromolecule assembly. Methods to tune and control orthogonal reactivity are also discussed, along with prospects for identifying new classes of compatible reactions. PMID: 26276062 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - August 10, 2015 Category: Biochemistry Authors: Patterson DM, Prescher JA Tags: Curr Opin Chem Biol Source Type: research

Synthetic histone code.
Abstract Chromatin is the universal template of genetic information in all eukaryotic cells. This complex of DNA and histone proteins not only packages and organizes genomes but also regulates gene expression. A multitude of posttranslational histone modifications and their combinations are thought to constitute a code for directing distinct structural and functional states of chromatin. Methods of protein chemistry, including protein semisynthesis, amber suppression technology, and cysteine bioconjugation, have enabled the generation of so-called designer chromatin containing histones in defined and homogeneous m...
Source: Current Opinion in Chemical Biology - August 5, 2015 Category: Biochemistry Authors: Fischle W, Mootz HD, Schwarzer D Tags: Curr Opin Chem Biol Source Type: research

Sustainability of biofuels and renewable chemicals production from biomass.
Abstract In the sectors of biofuel and renewable chemicals the big feedstock demand asks, first, to expand the spectrum of carbon sources beyond primary biomass, second, to establish circular processing chains and, third, to prioritize product sectors exclusively depending on carbon: chemicals and heavy-duty fuels. Large-volume production lines will reduce greenhouse gas (GHG) emission significantly but also low-volume chemicals are indispensable in building 'low-carbon' industries. The foreseeable feedstock change initiates innovation, securing societal wealth in the industrialized world and creating employment i...
Source: Current Opinion in Chemical Biology - August 5, 2015 Category: Biochemistry Authors: Kircher M Tags: Curr Opin Chem Biol Source Type: research

Multiply labeling proteins for studies of folding and stability.
Abstract Fluorescence spectroscopy is a powerful method for monitoring protein folding in real-time with high resolution and sensitivity, but requires the site-specific introduction of labels into the protein. The ability to genetically incorporate unnatural amino acids (Uaas) allows for the efficient synthesis of fluorescently labeled proteins with minimally perturbing fluorophores. Here, we describe recent uses of labeled proteins in dynamic structure determination experiments and advances in unnatural amino acid incorporation for dual site-specific fluorescent labeling. The advent of increasingly sophisticated ...
Source: Current Opinion in Chemical Biology - August 4, 2015 Category: Biochemistry Authors: Haney CM, Wissner RF, Petersson EJ Tags: Curr Opin Chem Biol Source Type: research

Editorial overview: Molecular imaging: Cellular imaging approaches.
PMID: 26238588 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - July 31, 2015 Category: Biochemistry Authors: Miyawaki A, Jaffrey SR Tags: Curr Opin Chem Biol Source Type: research

Biocatalysts for biomass deconstruction from environmental genomics.
Abstract Plant biomass offers a sustainable alternative to the energy and materials produced from fossil fuels. The industrial scale production or biorefining of fermentable sugars and aromatics from plant biomass is currently limited by the lack of cost effective and efficient biocatalysts. One potential solution to this problem is the discovery of biomass deconstructing biocatalysts from uncultivated microbial communities. Here we review recent progress in recovering such biological devices from environmental genomes and consider how this information can be used to build better biorefining ecosystems. PMID:...
Source: Current Opinion in Chemical Biology - July 28, 2015 Category: Biochemistry Authors: Armstrong Z, Mewis K, Strachan C, Hallam SJ Tags: Curr Opin Chem Biol Source Type: research

Synthetic approaches to protein phosphorylation.
Abstract Reversible protein phosphorylation is critically important in biology and medicine. Hundreds of thousands of sites of protein phosphorylation have been discovered but our understanding of the functions of the vast majority of these post-translational modifications is lacking. This review describes several chemical and biochemical methods that are under development and in current use to install phospho-amino acids and their mimics site-specifically into proteins. The relative merits of total chemical synthesis, semisynthesis, and nonsense suppression strategies for studying protein phosphorylation are disc...
Source: Current Opinion in Chemical Biology - July 17, 2015 Category: Biochemistry Authors: Chen Z, Cole PA Tags: Curr Opin Chem Biol Source Type: research

Repurposing the translation apparatus for synthetic biology.
Abstract The translation system (the ribosome and associated factors) is the cell's factory for protein synthesis. The extraordinary catalytic capacity of the protein synthesis machinery has driven extensive efforts to harness it for novel functions. For example, pioneering efforts have demonstrated that it is possible to genetically encode more than the 20 natural amino acids and that this encoding can be a powerful tool to expand the chemical diversity of proteins. Here, we discuss recent advances in efforts to expand the chemistry of living systems, highlighting improvements to the molecular machinery and genom...
Source: Current Opinion in Chemical Biology - July 14, 2015 Category: Biochemistry Authors: Des Soye BJ, Patel JR, Isaacs FJ, Jewett MC Tags: Curr Opin Chem Biol Source Type: research

Design of computational retrobiosynthesis tools for the design of de novo synthetic pathways.
Abstract Designing putative metabolic pathways is of great interest in synthetic biology. Retrobiosynthesis is a discipline that involves the design, evaluation, and optimization of de novo biosynthetic pathways for the production of high-value compounds and drugs from renewable resources and natural or engineered enzymes. The best candidate pathways are then engineered within a metabolic network of microorganisms that serve as synthetic platforms for synthetic biology. The complexity of biological chemistry and metabolism requires computational approaches to explore the full possibilities of engineering synthetic...
Source: Current Opinion in Chemical Biology - July 10, 2015 Category: Biochemistry Authors: Hadadi N, Hatzimanikatis V Tags: Curr Opin Chem Biol Source Type: research

Advances in de novo strain design using integrated systems and synthetic biology tools.
Abstract Recent efforts in expanding the range of biofuel and biorenewable molecules using microbial production hosts have focused on the introduction of non-native pathways in model organisms and the bio-prospecting of non-model organisms with desirable features. Current challenges lie in the assembly and coordinated expression of the (non-)native pathways and the elimination of competing pathways and undesirable regulation. Several systems and synthetic biology approaches providing contrasting top-down and bottom-up strategies, respectively, have been developed. In this review, we discuss recent advances in both...
Source: Current Opinion in Chemical Biology - July 9, 2015 Category: Biochemistry Authors: Ng CY, Khodayari A, Chowdhury A, Maranas CD Tags: Curr Opin Chem Biol Source Type: research

Butyrolactone signalling circuits for synthetic biology.
Abstract Signalling circuits based on quorum sensing mechanisms have been popular tools for synthetic biology. Recent advances in our understanding of the analogous systems regulating antibiotics production in soil bacteria suggest that these might provide useful complementary tools to increase the complexity of possible circuit designs. Here we discuss the diversity of these natural circuits, which use γ-butyrolactones (GBLs) as their main inter-cellular signal, highlighting the range of new building blocks they could provide, as well as a number of exciting recent applications of GBL-based circuits in hete...
Source: Current Opinion in Chemical Biology - July 8, 2015 Category: Biochemistry Authors: Biarnes-Carrera M, Breitling R, Takano E Tags: Curr Opin Chem Biol Source Type: research

Fast kinetics of calcium signaling and sensor design.
Abstract Fast calcium signaling is regulated by numerous calcium channels exhibiting high spatiotemporal profiles which are currently measured by fluorescent calcium sensors. There is still a strong need to improve the kinetics of genetically encoded calcium indicators (sensors) to capture calcium dynamics in the millisecond time frame. In this review, we summarize several major fast calcium signaling pathways and discuss the recent developments and application of genetically encoded calcium indicators to detect these pathways. A new class of genetically encoded calcium indicators designed with site-directed mutag...
Source: Current Opinion in Chemical Biology - July 4, 2015 Category: Biochemistry Authors: Tang S, Reddish F, Zhuo Y, Yang JJ Tags: Curr Opin Chem Biol Source Type: research