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

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

Fundamentals of ion mobility spectrometry.
Abstract Fundamental questions in ion mobility spectrometry have practical implications for analytical applications in general, and omics in particular, in three respects. (1) Understanding how ion mobility and collision cross section values depend on the collision gas, on the electric field and on temperature is crucial to ascertain their transferability across instrumental platforms. (2) Predicting collision cross section values for new analytes is necessary to exploit the full potential of ion mobility in discovery workflows. (3) Finally, understanding the fate of ion structures in the gas phase is essential to...
Source: Current Opinion in Chemical Biology - November 15, 2017 Category: Biochemistry Authors: Gabelica V, Marklund E Tags: Curr Opin Chem Biol Source Type: research

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Dynamic pathway regulation: recent advances and methods of construction.
Abstract Microbial cell factories are a renewable source for the production of biofuels and valuable chemicals. Dynamic pathway regulation has proved successful in improving production of molecules by balancing flux between growth of cells and production of metabolites. Systems for autonomous induction of pathway regulation are increasingly being developed, which include metabolite responsive promoters, biosensors, and quorum sensing systems. Since engineering such systems are dependent on the available methods for controlling protein abundance in the desired host, we review recent tools used for gene repression a...
Source: Current Opinion in Chemical Biology - October 20, 2017 Category: Biochemistry Authors: Tan SZ, Prather KL Tags: Curr Opin Chem Biol Source Type: research

Synthetic heparin and heparan sulfate: probes in defining biological functions.
Abstract Heparin and heparan sulfate are glycosaminoglycans that modulate numerous biological processes. The desire to capture the structural diversity responsible for their functions provides notable issues during synthesis, including site-selective sulfonation, stereoselective glycosylation and the sheer number of probable targets at hand. With current advances in synthetic approaches, carbohydrate chemists generate these complex targets by chemical and enzymatic methods. Fondaparinux and a number of polysaccharides have been synthesized to probe anticoagulation and other biological functions. Moreover, a trove ...
Source: Current Opinion in Chemical Biology - October 12, 2017 Category: Biochemistry Authors: Tsai CT, Zulueta MML, Hung SC Tags: Curr Opin Chem Biol Source Type: research

Synthetic plant glycans.
Abstract For more than a century the primary carbon source for the production of fuels, chemicals and many materials has been fossil resources. Recently, plant polysaccharides from non-food biomass have emerged as a promising renewable alternative that may displace a significant fraction of petroleum-derived products. As a food source, plant polysaccharides can provide beneficial effects on the human immune system in the form of dietary fiber. Despite the strong impact of plant glycans on society and human health, their chemical synthesis remains largely unexplored compared to the synthesis of mammalian and bacter...
Source: Current Opinion in Chemical Biology - October 9, 2017 Category: Biochemistry Authors: Pfrengle F Tags: Curr Opin Chem Biol Source Type: research

The plasticity of cyanobacterial carbon metabolism.
Abstract This opinion article aims to raise awareness of a fundamental issue which governs sustainable production of biofuels and bio-chemicals from photosynthetic cyanobacteria. Discussed is the plasticity of carbon metabolism, by which the cyanobacterial cells flexibly distribute intracellular carbon fluxes towards target products and adapt to environmental/genetic alterations. This intrinsic feature in cyanobacterial metabolism is being understood through recent identification of new biochemical reactions and engineering on low-throughput pathways. We focus our discussion on new insights into the nature of meta...
Source: Current Opinion in Chemical Biology - September 28, 2017 Category: Biochemistry Authors: Xiong W, Cano M, Wang B, Douchi D, Yu J Tags: Curr Opin Chem Biol Source Type: research

Peptide mediated formation of noble metal nanoparticles-controlling size and spatial arrangement.
Abstract Over the past two decades, peptides have expanded the toolbox of additives for the preparation of noble metal nanoparticles. Their functional and structural modularity and accompanying molecular recognition and self-assembly properties offer unique opportunities for the controlled formation of NPs. Within this review, we highlight recent examples for the use of peptides to control a) the size and shape of NPs and b) the spatial arrangement of NPs. The article focuses on examples where the peptides are directly involved in the bottom-up synthesis of the noble metal NPs. PMID: 28961470 [PubMed - as sup...
Source: Current Opinion in Chemical Biology - September 26, 2017 Category: Biochemistry Authors: Corra S, Shoshan MS, Wennemers H Tags: Curr Opin Chem Biol Source Type: research

Biosynthesis and structure-activity relationships of the lipid a family of glycolipids.
Abstract Lipopolysaccharide (LPS), a glycolipid found in the outer membrane of Gram-negative bacteria, is a potent elicitor of innate immune responses in mammals. A typical LPS molecule is composed of three different structural domains: a polysaccharide called the O-antigen, a core oligosaccharide, and Lipid A. Lipid A is the amphipathic glycolipid moiety of LPS. It stimulates the immune system by tightly binding to Toll-like receptor 4. More recently, Lipid A has also been shown to activate intracellular caspase-4 and caspase-5. An impressive diversity is observed in Lipid A structures from different Gram-negativ...
Source: Current Opinion in Chemical Biology - September 19, 2017 Category: Biochemistry Authors: Xiao X, Sankaranarayanan K, Khosla C Tags: Curr Opin Chem Biol Source Type: research

Light-induced functions in DNA.
necht HA Abstract The chemical toolbox for synthetic modification by nucleotide building blocks and postsynthetic methods delivers light-induced functions to DNA in great variety and allows not only to initiate photoinduced processes but additionally the temporal and spatial control of these artificial functions. Herein, selected light-induced artificial functions in DNA are briefly summarized. This includes the postsynthetic 'photoclick' labeling strategy, benzophenone and acetophenone nucleosides as photosensitizers to induce [2+2] cycloadditions, molecular switches and energy transfer based fluorophore pairs, c...
Source: Current Opinion in Chemical Biology - September 19, 2017 Category: Biochemistry Authors: Reisacher U, Antusch L, Hofsäß R, Schwechheimer C, Lehmann B, Wagenknecht HA Tags: Curr Opin Chem Biol Source Type: research

Needs and opportunities in bio-design automation: four areas for focus.
Abstract Bio-design automation (BDA) is an emerging field focused on computer-aided design, engineering principles, and automated manufacturing of biological systems. Here we discuss some outstanding challenges for bio-design that can be addressed by developing new tools for combinatorial engineering, equipment interfacing, next-generation sequencing, and workflow integration. These four areas, while not an exhaustive list of those that need to be addressed, could yield advances in bio-design, laboratory automation, and biometrology. PMID: 28923279 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - September 15, 2017 Category: Biochemistry Authors: Appleton E, Densmore D, Madsen C, Roehner N Tags: Curr Opin Chem Biol Source Type: research

Genetic code asymmetry supports diversity through experimentation with posttranslational modifications.
Abstract Protein N-glycosylation has been identified in all three domains of life presumably conserved for its early role in glycoprotein folding. However, the N-glycans added to proteins in the secretory pathway of multicellular organisms are remodeling in the Golgi, increasing structural diversity exponentially and adding new layers of functionality in immunity, metabolism and other systems. The branching and elongation of N-glycan chains found on cell surface receptors generates a gradation of affinities for carbohydrate-binding proteins, the galectin, selectin and siglec families. These interactions adapt cell...
Source: Current Opinion in Chemical Biology - September 15, 2017 Category: Biochemistry Authors: Dennis JW Tags: Curr Opin Chem Biol Source Type: research

An amino acid domino effect orchestrates ClpP's conformational states.
Abstract Maintaining the cellular protein homeostasis means managing life on the brink of death. This balance is largely based on precise fine-tuning of enzyme activities. For instance, the ClpP protease possesses several conformational switches which are fundamental to regulating its activity. Efforts have focused on revealing the structural basis of ClpP's conformational control. In the last decade, several amino acid clusters have been identified and functionally linked to specific activation states. Researchers have now begun to couple these hotspots to one another, uncovering a global network of residues that...
Source: Current Opinion in Chemical Biology - September 11, 2017 Category: Biochemistry Authors: Stahl M, Sieber SA Tags: Curr Opin Chem Biol Source Type: research

Synthetic zwitterionic polysaccharides.
;e JD Abstract Zwitterionic polysaccharides (ZPSs) are a unique class of polysaccharides that are capable of eliciting a T-cell response after being processed by antigen presenting cells and presented on MHC II molecules. In addition, they have also been shown to be potent stimulators of the innate arm of the immune system. To unravel the molecular details of their remarkable immunological activity, various synthetic approaches to assemble fragments towards these polysaccharides have been reported. This review describes these efforts, illustrating the immense challenges presented by these inspiring structures. ...
Source: Current Opinion in Chemical Biology - September 6, 2017 Category: Biochemistry Authors: Zhang Q, Overkleeft HS, van der Marel GA, Codée JD Tags: Curr Opin Chem Biol Source Type: research

Repurposing ribosomes for synthetic biology.
Abstract The translation system is the cell's factory for protein biosynthesis, stitching together hundreds to thousands of amino acids into proteins, which are required for the structure, function, and regulation of living systems. The extraordinary synthetic capability of this system, which includes the ribosome and its associated factors required for polymerization, has driven extensive efforts to harness it for societal use in areas as diverse as energy, materials, and medicine. A powerful example is recombinant protein production, which has impacted the lives of patients through the synthesis of biopharmaceut...
Source: Current Opinion in Chemical Biology - August 31, 2017 Category: Biochemistry Authors: Liu Y, Kim DS, Jewett MC Tags: Curr Opin Chem Biol Source Type: research

Primordial membranes: more than simple container boundaries.
Abstract Cellular membranes, which are self-assembled bilayer structures mainly composed of lipids, proteins and conjugated polysaccharides, are the defining feature of cell physiology. It is likely that the complexity of contemporary cells was preceded by simpler chemical systems or protocells during the various evolutionary stages that led from inanimate to living matter. It is also likely that primitive membranes played a similar role in protocell 'physiology'. The composition of such ancestral membranes has been proposed as mixtures of single hydrocarbon chain amphiphiles, which are simpler versions of modern ...
Source: Current Opinion in Chemical Biology - August 10, 2017 Category: Biochemistry Authors: Hanczyc MM, Monnard PA Tags: Curr Opin Chem Biol Source Type: research

Editorial overview: Chemical genetics and epigenetics.
PMID: 28801102 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - August 8, 2017 Category: Biochemistry Authors: Gavathiotis E, Zhou MM Tags: Curr Opin Chem Biol Source Type: research

Editorial overview: Molecular imaging for seeing chemistry in biology.
PMID: 28756083 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - July 26, 2017 Category: Biochemistry Authors: Chen X, Huang Y Tags: Curr Opin Chem Biol Source Type: research

Progress in targeting the BCL-2 family of proteins.
Abstract The network of protein-protein interactions among the BCL-2 protein family plays a critical role in regulating cellular commitment to mitochondrial apoptosis. Anti-apoptotic BCL-2 proteins are considered promising targets for drug discovery and exciting clinical progress has stimulated intense investigations in the broader family. Here, we discuss recent developments in small molecules targeting anti-apoptotic proteins and alternative approaches to targeting BCL-2 family interactions. These studies advance our understanding of the role of BCL-2 family proteins in physiology and disease, providing unique t...
Source: Current Opinion in Chemical Biology - July 20, 2017 Category: Biochemistry Authors: Garner TP, Lopez A, Reyna DE, Spitz AZ, Gavathiotis E Tags: Curr Opin Chem Biol Source Type: research

Synthetic antibody mimics for the inhibition of protein-ligand interactions.
er J Abstract The rational/structure-based design and/or combinatorial development of molecules capable of selectively binding to a protein, represents a promising strategy for a range of biomedical applications, in particular the inhibition of disease-associated protein-ligand interactions. The design of such protein binding molecules is often based on an antibody against the target protein, or involves the generation of smaller molecules that retain the binding characteristics of the antibody. Alternatively, protein binding molecules can be selected from protein libraries based on small, stably folded protein sc...
Source: Current Opinion in Chemical Biology - July 20, 2017 Category: Biochemistry Authors: Haußner C, Lach J, Eichler J Tags: Curr Opin Chem Biol Source Type: research

Advances of small molecule targeting of kinases.
n E Abstract Reversible protein phosphorylation regulates virtually all aspects of life in the cell. As a result, dysregulation of protein kinases, the enzymes responsible for transferring phosphate groups from ATP to proteins, are often the cause or consequence of many human diseases including cancer. Almost three dozen protein kinase inhibitors (PKIs) have been approved for clinical applications since 1995, the vast majority of them for the treatment of cancer. According to the NCI, there are more than 100 types of cancer. However, FDA-approved PKIs only target 14 of them. Importantly, of the more than 500 prote...
Source: Current Opinion in Chemical Biology - July 18, 2017 Category: Biochemistry Authors: Berndt N, Karim RM, Schönbrunn E Tags: Curr Opin Chem Biol Source Type: research

Advances in design of protein folds and assemblies.
ala R Abstract Conceptual and computational advances triggered an explosion of designed protein structures in the recent years. Various protein fold geometries have been robustly designed with atomic accuracy, including protein folds unseen in nature. The same principles and tools have been extended to design multi-chain assemblies. By exploiting symmetry, mega-Dalton structures have been created with exciting potential applications for synthetic biology. In this review we focus on design of single chain and multi polypeptide chain assemblies of defined size and composition. Several innovative strategies have been...
Source: Current Opinion in Chemical Biology - July 11, 2017 Category: Biochemistry Authors: Ljubetič A, Gradišar H, Jerala R Tags: Curr Opin Chem Biol Source Type: research

Allosteric regulation of epigenetic modifying enzymes.
Abstract Epigenetic enzymes including histone modifying enzymes are key regulators of gene expression in normal and disease processes. Many drug development strategies to target histone modifying enzymes have focused on ligands that bind to enzyme active sites, but allosteric pockets offer potentially attractive opportunities for therapeutic development. Recent biochemical studies have revealed roles for small molecule and peptide ligands binding outside of the active sites in modulating the catalytic activities of histone modifying enzymes. Here we highlight several examples of allosteric regulation of epigenetic...
Source: Current Opinion in Chemical Biology - July 6, 2017 Category: Biochemistry Authors: Zucconi BE, Cole PA Tags: Curr Opin Chem Biol Source Type: research

Chemical modulators for epigenome reader domains as emerging epigenetic therapies for cancer and inflammation.
Abstract Site-specific lysine acetylation and methylation on histones are critical post-translational modifications (PTMs) that govern ordered gene transcription in chromatin. Mis-regulation of these histone PTM-mediated processes has been shown to be associated with human diseases. Since the 2010 landmark reports of small molecules (+)-JQ1 and I-BET762 that target the acetyl-lysine 'reader' Bromodomain and Extra Terminal domain (BET) proteins, there have been relentless efforts to develop epigenetic therapy with small molecules to modulate molecular interactions of epigenome reader domain proteins with PTMs. In a...
Source: Current Opinion in Chemical Biology - July 6, 2017 Category: Biochemistry Authors: Zaware N, Zhou MM Tags: Curr Opin Chem Biol Source Type: research

Recent progress in developing selective inhibitors of protein methyltransferases.
n J Abstract Mounting evidence suggests that protein methyltransferases (PMTs), which catalyze methylation of histones as well as non-histone proteins, play a crucial role in diverse biological pathways and human diseases. In particular, PMTs have been recognized as major players in regulating gene expression and chromatin state. There has been an increasingly growing interest in these enzymes as potential therapeutic targets and over the past two years tremendous progress has been made in the discovery of selective, small molecule inhibitors of protein lysine and arginine methyltransferases. Inhibitors of PMTs ha...
Source: Current Opinion in Chemical Biology - June 26, 2017 Category: Biochemistry Authors: Kaniskan HÜ, Jin J Tags: Curr Opin Chem Biol Source Type: research

Small molecule probes of protein aggregation.
Abstract Understanding the mechanisms of amyloid formation and toxicity remain major challenges. Although substantial progress has been made in the development of methods able to identify the species formed during self-assembly and to describe the kinetic mechanisms of aggregation, the structure(s) of non-native species, including potentially toxic oligomers, remain elusive. Moreover, how fibrils contribute to disease remains unclear. Here we review recent advances in the development of small molecules and other reagents that are helping to define the mechanisms of protein aggregation in molecular detail. Such pro...
Source: Current Opinion in Chemical Biology - June 22, 2017 Category: Biochemistry Authors: Young LM, Ashcroft AE, Radford SE Tags: Curr Opin Chem Biol Source Type: research

Lipid homeostasis and regulated cell death.
This article highlights how the lipid composition of membranes determines specific organelle functions, how homeostatic mechanisms maintain these functions by regulating physical properties of membranes, and how cells disrupt lipid homeostasis to bring about regulated cell death (RCD). These are broad phenomena, and representative examples are reviewed here. In particular, the mechanisms of ferroptosis - a form of RCD brought about by lipid peroxidation - are highlighted, demonstrating how lipid metabolism drives cells' lipid composition toward states of increased sensitivity to lipid oxidation. An understanding of these i...
Source: Current Opinion in Chemical Biology - June 20, 2017 Category: Biochemistry Authors: Agmon E, Stockwell BR Tags: Curr Opin Chem Biol Source Type: research

Progress in programming spatiotemporal patterns and machine-assembly in cell-free protein expression systems.
Abstract Building biological systems outside the cell is an emerging interdisciplinary research field aimed to study design principles, and to emulate biological functions for technology. Reconstructing programmable cellular functions, from assembly of protein/nucleic-acid machines to spatially distributed systems, requires implementing minimal systems of molecular interactions encoded in genes, source-sink protein expression dynamics, and materials platforms for reaction-diffusion scenarios. Here, we first review how molecular turnover mechanisms, combined with nonlinear interactions and feedback in cell-free gen...
Source: Current Opinion in Chemical Biology - June 16, 2017 Category: Biochemistry Authors: Tayar AM, Daube SS, Bar-Ziv RH Tags: Curr Opin Chem Biol Source Type: research

Mammalian synthetic biology in the age of genome editing and personalized medicine.
Abstract The recent expansion of molecular tool kits has propelled synthetic biology toward the design of increasingly sophisticated mammalian systems. Specifically, advances in genome editing, protein engineering, and circuitry design have enabled the programming of cells for diverse applications, including regenerative medicine and cancer immunotherapy. The ease with which molecular and cellular interactions can be harnessed promises to yield novel approaches to elucidate genetic interactions, program cellular functions, and design therapeutic interventions. Here, we review recent advancements in the development...
Source: Current Opinion in Chemical Biology - June 16, 2017 Category: Biochemistry Authors: Ho P, Chen YY Tags: Curr Opin Chem Biol Source Type: research

Small molecule probes for cellular death machines.
Abstract The past decade has witnessed a significant expansion of our understanding about the regulated cell death mechanisms beyond apoptosis. The application of chemical biological approaches had played a major role in driving these exciting discoveries. The discovery and use of small molecule probes in cell death research has not only revealed significant insights into the regulatory mechanism of cell death but also provided new drug targets and lead drug candidates for developing therapeutics of human diseases with huge unmet need. Here, we provide an overview of small molecule modulators for necroptosis and f...
Source: Current Opinion in Chemical Biology - June 16, 2017 Category: Biochemistry Authors: Li Y, Qian L, Yuan J Tags: Curr Opin Chem Biol Source Type: research

Recent advances in synthetic biology for engineering isoprenoid production in yeast.
Abstract Isoprenoids (terpenes/terpenoids) have many useful industrial applications, but are often not produced at industrially viable level in their natural sources. Synthetic biology approaches have been used extensively to reconstruct metabolic pathways in tractable microbial hosts such as yeast and re-engineer pathways and networks to increase yields. Here we review recent advances in this field, focusing on central carbon metabolism engineering to increase precursor supply, re-directing carbon flux for production of C10, C15, or C20 isoprenoids, and chemical decoration of high value diterpenoids (C20). We als...
Source: Current Opinion in Chemical Biology - June 14, 2017 Category: Biochemistry Authors: Vickers CE, Williams TC, Peng B, Cherry J Tags: Curr Opin Chem Biol Source Type: research