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

Quantitative microscopy based on single-molecule fluorescence.
Abstract Quantitative microscopy is needed to understand reactions or phenomena carried out by biological molecules such as enzymes, receptors, and membrane-localized proteins. Counting the biomolecules of interest in single organelles or cellular compartments is critical in these approaches. In this brief perspective, we focus on the development of quantitative fluorescence microscopies that measure the precise copy numbers of proteins in cellular organelles or purified samples. We introduce recent improvements in quantitative microscopies to overcome undercounting or overcounting errors in certain conditions. We...
Source: Current Opinion in Chemical Biology - June 14, 2017 Category: Biochemistry Authors: Jung SR, Fujimoto BS, Chiu DT Tags: Curr Opin Chem Biol Source Type: research

Covalent inhibitors: an opportunity for rational target selectivity.
Abstract There is a resurging interest in compounds that engage their target through covalent interactions. Cysteine's thiol is endowed with enhanced reactivity, making it the nucleophile of choice for covalent engagement with a ligand aligning an electrophilic trap with a cysteine residue in a target of interest. The paucity of cysteine in the proteome coupled to the fact that closely related proteins do not necessarily share a given cysteine residue enable a level of unprecedented rational target selectivity. The recent demonstration that a lysine's amine can also be engaged covalently with a mild electrophile e...
Source: Current Opinion in Chemical Biology - June 10, 2017 Category: Biochemistry Authors: Lagoutte R, Patouret R, Winssinger N Tags: Curr Opin Chem Biol Source Type: research

Sense and sensitivity in bioprocessing-detecting cellular metabolites with biosensors.
Abstract Biosensors use biological elements to detect or quantify an analyte of interest. In bioprocessing, biosensors are employed to monitor key metabolites. There are two main types: fully biological systems or biological recognition coupled with physical/chemical detection. New developments in chemical biosensors include multiplexed detection using microfluidics. Synthetic biology can be used to engineer new biological biosensors with improved characteristics. Although there have been few biosensors developed for bioprocessing thus far, emerging trends can be applied in the future. A range of new platform tech...
Source: Current Opinion in Chemical Biology - June 10, 2017 Category: Biochemistry Authors: Dekker L, Polizzi KM Tags: Curr Opin Chem Biol Source Type: research

Targeted protein knockdown using small molecule degraders.
Abstract Small molecule probes of biological systems have traditionally been designed to bind to and inhibit the active sites of their protein targets. While this class of pharmacological agents has been broadened by the development of a small number of allosteric and protein-protein interaction (PPI) inhibitors, conventional drug design still excludes 'undruggable' proteins that are neither enzymes nor receptors. Recent years have seen the emergence of new classes of small molecules that can target hitherto undruggable proteins by recruiting the cellular proteostasis machinery to selectively tag them for degradat...
Source: Current Opinion in Chemical Biology - June 9, 2017 Category: Biochemistry Authors: Raina K, Crews CM Tags: Curr Opin Chem Biol Source Type: research

Visualizing glycans on single cells and tissues-Visualizing glycans on single cells and tissues.
Abstract Metabolic oligosaccharide engineering and chemoenzymatic glycan labeling have provided powerful tools to study glycans in living systems and tissue samples. In this review article, we summarize recent advances in this field with a focus on innovative approaches for glycan imaging. The presented applications demonstrate that several of the leading imaging methods, which have revolutionized quantitative cell biology, can be adapted to imaging glycans on single cells and tissues. PMID: 28578260 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - June 1, 2017 Category: Biochemistry Authors: Ovryn B, Li J, Hong S, Wu P Tags: Curr Opin Chem Biol Source Type: research

Cyclic peptide natural products chart the frontier of oral bioavailability in the pursuit of undruggable targets.
Abstract As interest in protein-protein interactions and other previously-undruggable targets increases, medicinal chemists are returning to natural products for design inspiration toward molecules that transcend the paradigm of small molecule drugs. These compounds, especially peptides, often have poor ADME properties and thus require a more nuanced understanding of structure-property relationships to achieve desirable oral bioavailability. Although there have been few clinical successes in this chemical space to date, recent work has identified opportunities to introduce favorable physicochemical properties to p...
Source: Current Opinion in Chemical Biology - May 29, 2017 Category: Biochemistry Authors: Naylor MR, Bockus AT, Blanco MJ, Lokey RS Tags: Curr Opin Chem Biol Source Type: research

Blood-brain barrier peptide shuttles.
dó M Abstract Brain delivery is hampered by the presence of the blood-brain barrier (BBB), a natural defence of the brain that protects it and allows the entrance of nutrients by several mechanisms. Taking advantage of these mechanisms is an opportunity to treat brain related diseases. Among the different alternatives, BBB peptide shuttles are gaining attention to increase brain delivery of therapeutics. The most recent advances in the field are analysed here. PMID: 28558293 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - May 27, 2017 Category: Biochemistry Authors: Sánchez-Navarro M, Giralt E, Teixidó M Tags: Curr Opin Chem Biol Source Type: research

Quantitative chemical imaging with stimulated Raman scattering microscopy.
Abstract Chemical imaging plays an increasingly important role in studying heterogeneous biological systems. It combines molecular spectroscopy with high-resolution spatial information to create quantitative images of molecular distributions. Here I summarize recent progress in technical developments and biological applications of a specific chemical imaging technique-stimulated Raman scattering (SRS) microscopy. SRS microscopy allows for a wide range of molecules - both endogenous and exogenous - to be imaged at high spatial and temporal resolution in living cells, tissues, and organisms. I will focus on developm...
Source: Current Opinion in Chemical Biology - May 22, 2017 Category: Biochemistry Authors: Fu D Tags: Curr Opin Chem Biol Source Type: research

Development of photostable fluorophores for molecular imaging.
Abstract Advances in fluorescence microscopy promise to unlock details of biological systems with high spatiotemporal precision. These new techniques also place a heavy demand on the 'photon budget'-the number of photons one can extract from a sample. Improving the photostability of small molecule fluorophores using chemistry is a straightforward method for increasing the photon budget. Here, we review the (sometimes sparse) efforts to understand the mechanism of fluorophore photobleaching and recent advances to improve photostability through reducing the propensity for oxidation or through intramolecular triplet-...
Source: Current Opinion in Chemical Biology - May 22, 2017 Category: Biochemistry Authors: Zheng Q, Lavis LD Tags: Curr Opin Chem Biol Source Type: research

Fluorescent probes for imaging formaldehyde in biological systems.
Abstract Formaldehyde (FA) is a common environmental toxin but is also endogenously produced through a diverse array of essential biological processes, including mitochondrial one-carbon metabolism, metabolite oxidation, and nuclear epigenetic modifications. Its high electrophilicity enables reactivity with a wide variety of biological nucleophiles, which can be beneficial or detrimental to cellular function depending on the context. New methods that enable detection of FA in living systems can help disentangle the signal/stress dichotomy of this simplest reactive carbonyl species (RCS), and fluorescent probes for...
Source: Current Opinion in Chemical Biology - May 18, 2017 Category: Biochemistry Authors: Bruemmer KJ, Brewer TF, Chang CJ Tags: Curr Opin Chem Biol Source Type: research

Structure-diverse Phylomer libraries as a rich source of bioactive hits from phenotypic and target directed screens against intracellular proteins.
Abstract Phylomers are peptides derived from biodiverse protein fragments. Genetically encoded Phylomer libraries have been constructed, containing hundreds of billions of peptides derived from virtually all of the few thousand fold families found in the protein universe. They offer a rich source of high quality hits against diverse target sequences and have been used for three main purposes: firstly, to identify and validate targets in phenotypic screens; secondly, to block protein interactions with nanomolar potency binding affinities; thirdly as a source of more efficient cell penetrating peptides for the deliv...
Source: Current Opinion in Chemical Biology - May 18, 2017 Category: Biochemistry Authors: Watt PM, Milech N, Stone SR Tags: Curr Opin Chem Biol Source Type: research

Engineering genetically-encoded tools for optogenetic control of protein activity.
Abstract Optogenetic tools offer fast and reversible control of protein activity with subcellular spatial precision. In the past few years, remarkable progress has been made in engineering photoactivatable systems regulating the activity of cellular proteins. In this review, we discuss general strategies in designing and optimizing such optogenetic tools and highlight recent advances in the field, with specific focus on applications regulating protein catalytic activity. PMID: 28527343 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - May 17, 2017 Category: Biochemistry Authors: Liu Q, Tucker CL Tags: Curr Opin Chem Biol Source Type: research

Harnessing plant metabolic diversity.
Abstract Advances in DNA sequencing and synthesis technologies in the twenty-first century are now making it possible to build large-scale pipelines for engineering plant natural product pathways into heterologous production species using synthetic biology approaches. The ability to decode the chemical potential of plants by sequencing their transcriptomes and/or genomes and to then use this information as an instruction manual to make drugs and other high-value chemicals is opening up new routes to harness the vast chemical diversity of the Plant Kingdom. Here we describe recent progress in methods for pathway di...
Source: Current Opinion in Chemical Biology - May 17, 2017 Category: Biochemistry Authors: Owen C, Patron NJ, Huang A, Osbourn A Tags: Curr Opin Chem Biol Source Type: research

Synchrotron-based X-ray microscopy for sub-100nm resolution cell imaging.
Abstract Microscopic imaging provides a straightforward approach to deepen our understanding of cellular events. While the resolution of optical microscopes is generally limited to 200-300nm due to the diffraction limit, there has been ever growing interest in studying cells at the sub-100nm regime. By exploiting the short wavelength, long penetration depth and elemental specificity of X-rays, synchrotron-based X-ray microscopy (XRM) has demonstrated its power in exploring the structure and function of cells at the nanometer resolution. Here we summarize recent advances in using XRM for imaging ultrastructure of o...
Source: Current Opinion in Chemical Biology - May 15, 2017 Category: Biochemistry Authors: Zhu Y, Zhang J, Li A, Zhang Y, Fan C Tags: Curr Opin Chem Biol Source Type: research

Combinatorial chemistry in drug discovery.
Abstract Several combinatorial methods have been developed to create focused or diverse chemical libraries with a wide range of linear or macrocyclic chemical molecules: peptides, non-peptide oligomers, peptidomimetics, small-molecules, and natural product-like organic molecules. Each combinatorial approach has its own unique high-throughput screening and encoding strategy. In this article, we provide a brief overview of combinatorial chemistry in drug discovery with emphasis on recently developed new technologies for design, synthesis, screening and decoding of combinatorial library. Examples of successful applic...
Source: Current Opinion in Chemical Biology - May 8, 2017 Category: Biochemistry Authors: Liu R, Li X, Lam KS Tags: Curr Opin Chem Biol Source Type: research

Designer probiotics for the prevention and treatment of human diseases.
Abstract Various studies have shown the beneficial effects of probiotics in humans. The use of synthetic biology to engineer programmable probiotics that specifically targets cancer, infectious agents, or other metabolic diseases has gained much interest since the last decade. Developments made in synthetic probiotics as therapeutics within the last three years will be discussed in this review. PMID: 28478369 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - May 4, 2017 Category: Biochemistry Authors: Chua KJ, Kwok WC, Aggarwal N, Sun T, Chang MW Tags: Curr Opin Chem Biol Source Type: research

A three-step framework for programming pattern formation.
Abstract The spatial organisation of gene expression is essential to create structure and function in multicellular organisms during developmental processes. Such organisation occurs by the execution of algorithmic functions, leading to patterns within a given domain, such as a tissue. Engineering these processes has become increasingly important because bioengineers are seeking to develop tissues ex vivo. Moreover, although there are several theories on how pattern formation can occur in vivo, the biological relevance and biotechnological potential of each of these remains unclear. In this review, we will briefly...
Source: Current Opinion in Chemical Biology - April 29, 2017 Category: Biochemistry Authors: Scholes NS, Isalan M Tags: Curr Opin Chem Biol Source Type: research

Voltage imaging with genetically encoded indicators.
Abstract Membrane voltages are ubiquitous throughout cell biology. Voltage is most commonly associated with excitable cells such as neurons and cardiomyocytes, although many other cell types and organelles also support electrical signaling. Voltage imaging in vivo would offer unique capabilities in reporting the spatial pattern and temporal dynamics of electrical signaling at the cellular and circuit levels. Voltage is not directly visible, and so a longstanding challenge has been to develop genetically encoded fluorescent voltage indicator proteins. Recent advances have led to a profusion of new voltage indicator...
Source: Current Opinion in Chemical Biology - April 28, 2017 Category: Biochemistry Authors: Xu Y, Zou P, Cohen AE Tags: Curr Opin Chem Biol Source Type: research

Plant viruses and bacteriophages for delivery in medicine and biotechnology.
Abstract There are a wide variety of synthetic and naturally occurring nanomaterials under development for nanoscale cargo-delivery applications. Viruses play a special role in these developments, because they can be regarded as naturally occurring nanomaterials evolved to package and deliver cargos. While any nanomaterial has its advantage and disadvantages, viral nanoparticles (VNPs), in particular the ones derived from plant viruses and bacteriophages, are attractive options for cargo-delivery as they are biocompatible, biodegradable, and non-infectious to mammals. Their protein-based structures are often under...
Source: Current Opinion in Chemical Biology - April 17, 2017 Category: Biochemistry Authors: Czapar AE, Steinmetz NF Tags: Curr Opin Chem Biol Source Type: research

Peptide blockers of Kv1.3 channels in T cells as therapeutics for autoimmune disease.
We describe their structures, their binding site in the external vestibule of Kv1.3, how they have been engineered to improve Kv1.3-specificity, and their pharmacokinetic and pharmacodynamic properties. Finally, we highlight the therapeutic potential of Kv1.3 peptide inhibitors to treat autoimmune diseases without compromising protective immune responses. PMID: 28412597 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - April 13, 2017 Category: Biochemistry Authors: Chandy KG, Norton RS Tags: Curr Opin Chem Biol Source Type: research

Host defense antimicrobial peptides as antibiotics: design and application strategies.
Abstract This review deals with the design and application strategies of new antibiotics based on naturally occurring antimicrobial peptides (AMPs). The initial candidate can be designed based on three-dimensional structure or selected from a library of peptides from natural or laboratory sources followed by optimization via structure-activity relationship studies. There are also advanced application strategies such as induction of AMP expression from host cells by various factors (e.g., metals, amino acids, vitamin D and sunlight), the use of engineered probiotic bacteria to deliver peptides, the design of prodru...
Source: Current Opinion in Chemical Biology - April 8, 2017 Category: Biochemistry Authors: Mishra B, Reiling S, Zarena D, Wang G Tags: Curr Opin Chem Biol Source Type: research

Exploring sequence space in search of functional enzymes using microfluidic droplets.
Abstract Screening of enzyme mutants in monodisperse picoliter compartments, generated at kilohertz speed in microfluidic devices, is coming of age. After a decade of proof-of-principle experiments, workflows have emerged that combine existing microfluidic modules to assay reaction progress quantitatively and yield improved enzymes. Recent examples of the screening of libraries of randomised proteins and from metagenomic sources suggest that this approach is not only faster and cheaper, but solves problems beyond the feasibility scope of current methodologies. The establishment of new assays in this format - so fa...
Source: Current Opinion in Chemical Biology - April 5, 2017 Category: Biochemistry Authors: Mair P, Gielen F, Hollfelder F Tags: Curr Opin Chem Biol Source Type: research