Biosynthesis of pyranonaphthoquinone polyketides reveals diverse strategies for enzymatic carbon-carbon bond formation.
inose K Abstract Pyranonaphthoquinones synthesized by Streptomyces bacteria via type II polyketide pathways are aromatic compounds build around a common three-ring structure, which is composed of pyran, quinone and benzene rings. Over the years, actinorhodin in particular has served as a model compound for studying the biosynthesis of aromatic polyketides, while some of the other metabolites such as granaticin, medermycin, frenolicin and alnumycin A have enabled comparative studies that complement our understanding how these complex biological systems function and have evolved. In addition, despite the similarity ...
Source: Current Opinion in Chemical Biology - July 22, 2013 Category: Biochemistry Authors: Metsä-Ketelä M, Oja T, Taguchi T, Okamoto S, Ichinose K Tags: Curr Opin Chem Biol Source Type: research

Photoswitchable fluorescent proteins: ten years of colorful chemistry and exciting applications.
Abstract Reversibly photoswitchable fluorescent proteins (RSFPs) are fluorescent proteins whose fluorescence, upon excitation at a certain wavelength, can be switched on or off by light in a reversible manner. In the last 10 years, many new RSFPs have been developed and novel applications in cell imaging discovered that rely on their photoswitching properties. This review will describe research on the mechanisms of reversible photoswitching and recent applications using RSFPs. While cis-trans isomerization of the chromophore is believed to be the general mechanism for most RSFPs, structural studies reveal diversit...
Source: Current Opinion in Chemical Biology - July 19, 2013 Category: Biochemistry Authors: Zhou XX, Lin MZ Tags: Curr Opin Chem Biol Source Type: research

Biomolecular analysis with microring resonators: applications in multiplexed diagnostics and interaction screening.
Abstract Microring optical resonators are a promising class of sensor whose value in bioanalytical applications has only begun to be explored. Utilized in the telecommunication industry for signal processing applications, microring resonators have more recently been re-tasked for biosensing because of their scalability, sensitivity, and versatility. Their sensing modality arises from light/matter interactions-light propagating through the microring and the resultant evanescent field extending beyond the structure is sensitive to the refractive index of the local environment, which modulates resonant wavelength of ...
Source: Current Opinion in Chemical Biology - July 17, 2013 Category: Biochemistry Authors: Kindt JT, Bailey RC Tags: Curr Opin Chem Biol Source Type: research

Phosphonate biosynthesis and catabolism: a treasure trove of unusual enzymology.
Abstract Natural product biosynthesis has proven a fertile ground for the discovery of novel chemistry. Herein we review the progress made in elucidating the biosynthetic pathways of phosphonate and phosphinate natural products such as the antibacterial compounds dehydrophos and fosfomycin, the herbicidal phosphinothricin-containing peptides, and the antimalarial compound FR-900098. In each case, investigation of the pathway has yielded unusual, and often unprecedented, biochemistry. Likewise, recent investigations have uncovered novel ways to cleave the CP bond to yield phosphate under phosphorus starvation condi...
Source: Current Opinion in Chemical Biology - July 16, 2013 Category: Biochemistry Authors: Peck SC, van der Donk WA Tags: Curr Opin Chem Biol Source Type: research

Chemical mechanisms involved during the biosynthesis of tropolones.
Abstract Tropolones are seven-membered aromatic rings which feature in the core of several important bioactive natural products including colchicine and stipitatic acid. Studies of their biosynthesis over nearly 70 years have revealed four parallel routes from polyketide, terpene, alkaloid and shikimate precursors, but the key steps all involve ring expansion of an alkylated 6-membered ring. Recent studies in fungi have revealed details of the individual chemical steps at the molecular level, but detailed molecular biosynthetic pathways in other organisms remain obscure. PMID: 23870699 [PubMed - as supplied b...
Source: Current Opinion in Chemical Biology - July 16, 2013 Category: Biochemistry Authors: Cox RJ, Al-Fahad A Tags: Curr Opin Chem Biol Source Type: research

Ion mobility-mass spectrometry of intact protein-ligand complexes for pharmaceutical drug discovery and development.
Abstract Mass spectrometry (MS) plays a number of key roles in the discovery and development phases for modern pharmaceutical compounds, ranging from the assessment of protein-ligand binding to biomarker discovery. Historically, however, MS has had a relatively limited role in the drug discovery process in comparison to high-throughput fluorescence and radiometric screens. This picture may be changing, however, as many presumptive protein targets are coupled to human disease pathways through specific protein-protein interactions and protein conformations, rather than enzyme activities. This fact will likely drive ...
Source: Current Opinion in Chemical Biology - July 12, 2013 Category: Biochemistry Authors: Niu S, Rabuck JN, Ruotolo BT Tags: Curr Opin Chem Biol Source Type: research

Echinomycin biosynthesis.
Abstract Echinomycin is an antitumor antibiotic secondary metabolite isolated from streptomycetes, whose core structure is biosynthesized by nonribosomal peptide synthetase (NRPS). The echinomycin biosynthetic pathway was successfully reconstituted in Escherichia coli. NRPS often contains a thioesterase domain at its C terminus for cyclorelease of the elongating peptide chain. Those thioesterase domains were shown to exhibit significant substrate tolerance. More recently, an oxidoreductase Ecm17, which forms the disulfide bridge in triostin A, was characterized. Surprisingly, an unrelated disulfide-forming enzyme ...
Source: Current Opinion in Chemical Biology - July 12, 2013 Category: Biochemistry Authors: Sato M, Nakazawa T, Tsunematsu Y, Hotta K, Watanabe K Tags: Curr Opin Chem Biol Source Type: research

Dot by dot: analyzing the glycome using lectin microarrays.
Abstract The glycome, that is, the cohort of carbohydrates within a cell or tissue, plays a key part in diverse biological interactions involved in health and disease. Glycans are structurally complex and notoriously difficult to analyze. Lectin microarrays, a sensitive and high-throughput method for glycomic profiling, provide a global view of the glycome. In recent work, this technology has been successfully applied to a wide range of studies, from identification of glycan-based stem cell markers to the detection of pathogens and early diagnosis of disease. This review focuses on advances in the field of lectin ...
Source: Current Opinion in Chemical Biology - July 12, 2013 Category: Biochemistry Authors: Ribeiro JP, Mahal LK Tags: Curr Opin Chem Biol Source Type: research

Emerging trends in in vivo neurochemical monitoring by microdialysis.
Abstract Mapping chemical dynamics in the brain of live subjects is a challenging but highly rewarding goal because it allows neurotransmitter fluctuations to be related to behavior, drug effects, and disease states. A popular method for such measurements is microdialysis sampling coupled to analytical measurements. This method has become well-established for monitoring low molecular weight neurotransmitters, metabolites, and drugs, especially in pharmacological and pharmacokinetic studies. Recent technological developments which improve the temporal and spatial resolution of the methods will enable it to be used ...
Source: Current Opinion in Chemical Biology - July 12, 2013 Category: Biochemistry Authors: Kennedy RT Tags: Curr Opin Chem Biol Source Type: research

Radical mediated ring formation in the biosynthesis of the hypermodified tRNA base wybutosine.
Abstract Wyosine and its derivatives are highly modified, acid labile tricyclic bases found at position 37 of tRNA(Phe) in archaea and eukarya. The formation of the common 4-demethylwyosine structural feature entails condensation of pyruvate and N-methylguanosine catalyzed by TYW1. This review will focus on the mechanism of this complex radical mediated transformation. PMID: 23856057 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - July 12, 2013 Category: Biochemistry Authors: Young AP, Bandarian V Tags: Curr Opin Chem Biol Source Type: research

The path of lysine to pyrrolysine.
Abstract Pyrrolysine is the 22nd genetically encoded amino acid. For many years, its biosynthesis has been primarily a matter for conjecture. Recently, a pathway for the synthesis of pyrrolysine from two molecules of lysine was outlined in which a radical SAM enzyme acts as a lysine mutase to generate a methylated ornithine from lysine, which is then ligated to form an amide with the ɛ-amine of a second lysine. Oxidation of the isopeptide gives rise to pyrrolysine. Mechanisms have been proposed for both the mutase and the ligase, and structures now exist for each, setting the stage for a more detailed understandi...
Source: Current Opinion in Chemical Biology - July 12, 2013 Category: Biochemistry Authors: Krzycki JA Tags: Curr Opin Chem Biol Source Type: research

Human metabolomics: strategies to understand biology.
Abstract Metabolomics provides a direct functional read-out of the physiological status of an organism and is in principle ideally suited to describe someone's health status. Whereas only a limited number of small metabolites are used in the clinics, in inborn errors of metabolism an extensive repertoire of metabolites are used as biomarkers. We discuss that the proper clinical phenotyping is crucial to find biomarkers and obtain biological insights for multifactorial diseases. This requires to study the phenotype dynamics including the concepts of homeostasis and allostasis, that is, the ability to adapt and cope...
Source: Current Opinion in Chemical Biology - July 9, 2013 Category: Biochemistry Authors: Ramautar R, Berger R, van der Greef J, Hankemeier T Tags: Curr Opin Chem Biol Source Type: research

Opportunities and challenges from current investigations into the biosynthetic logic of nosiheptide-represented thiopeptide antibiotics.
Abstract Nosiheptide is an archetypal thiopeptide antibiotic, possessing a characteristic macrocyclic core that contains a 6-membered heterocycle central to multiple azol(in)es and dehydroamino acids. The discovery of the ribosomal origin of thiopeptides revealed a unifying theme, showing that the structural complexity arises from post-translational modifications (PTMs) of precursor peptides. Thiopeptide framework formation proceeds via cyclodehydration/dehydrogenation (for azol(in)es), dehydration (for dehydroamino acids), and cycloaddition (for the central heterocycle domain). This common process has not been re...
Source: Current Opinion in Chemical Biology - July 6, 2013 Category: Biochemistry Authors: Wang S, Zhou S, Liu W Tags: Curr Opin Chem Biol Source Type: research

New generation of oral mucosal vaccines targeting dendritic cells.
Abstract As most infectious organisms gain entry at mucosal surfaces, there is a great deal of interest in developing vaccines that elicit effective mucosal immune responses against pathogen challenge. Targeted vaccination is one of the most effective methods available to prevent and control infectious diseases. Mucosal vaccines can offer lower costs, better accessibility, needle free delivery, and a higher capacity for mass immunizations during pandemics. Both local mucosal immunity and robust systemic responses can be achieved through mucosal vaccination. Recent progress in understanding the molecular and cellul...
Source: Current Opinion in Chemical Biology - July 5, 2013 Category: Biochemistry Authors: Owen JL, Sahay B, Mohamadzadeh M Tags: Curr Opin Chem Biol Source Type: research

Radical SAM-mediated methylation reactions.
Abstract A subset of enzymes that belong to the radical S-adenosylmethionine (SAM) superfamily is able to catalyze methylation reactions. Substrates of these enzymes are distinct from the nucleophilic substrates that undergo methylation by a polar mechanism. Recently, activities of several radical SAM methylating enzymes have been reconstituted in vitro and their mechanisms of catalysis investigated. The RNA modifying enzymes RlmN and Cfr catalyze methylation via a methyl synthase mechanism. These enzymes use SAM in two distinct roles: as a source of a methyl group transferred to a conserved cysteine and as a sour...
Source: Current Opinion in Chemical Biology - July 5, 2013 Category: Biochemistry Authors: Fujimori DG Tags: Curr Opin Chem Biol Source Type: research

Quantifying proteomes and their post-translational modifications by stable isotope label-based mass spectrometry.
Abstract Stable isotope labeling coupled with mass spectrometry has revolutionized the scope and impact of protein expression studies. Label incorporation can occur metabolically or chemically, and each method bears specific strengths and weaknesses. Quantitative proteomics confidently identifies specific interactions between proteins and other biological species, such as nucleic acids and metabolites. Extending label-based methods to phosphorylation-modified forms of proteins enables the construction of signaling networks and their temporal responses to stimuli. The integration of multiple data types offers syste...
Source: Current Opinion in Chemical Biology - July 5, 2013 Category: Biochemistry Authors: Merrill AE, Coon JJ Tags: Curr Opin Chem Biol Source Type: research

Lipidomics from an analytical perspective.
Abstract The global non-targeted analysis of various biomolecules in a variety of sample sources gained momentum in recent years. Defined as the study of the full lipid complement of cells, tissues and organisms, lipidomics is currently evolving out of the shadow of the more established omics sciences including genomics, transcriptomics, proteomics and metabolomics. In analogy to the latter, lipidomics has the potential to impact on biomarker discovery, drug discovery/development and system knowledge, amongst others. The tools developed by lipid researchers in the past, complemented with the enormous advancements ...
Source: Current Opinion in Chemical Biology - July 3, 2013 Category: Biochemistry Authors: Sandra K, Sandra P Tags: Curr Opin Chem Biol Source Type: research

The enzymatic conversion of phosphonates to phosphate by bacteria.
Abstract Phosphonates are ubiquitous organophosphorus compounds that contain a characteristic CP bond which is chemically inert and hydrolytically stable. Bacteria have evolved pathways to metabolize these phosphonate compounds and utilize the products of these pathways as nutrient sources. This review aims to present all of the known bacterial enzymes capable of transforming phosphonates to phosphates. There are three major classes of enzymes known to date performing such transformations: phosphonatases, the C-P lyase complex and an oxidative pathway for CP bond cleavage. A brief description of each class is pres...
Source: Current Opinion in Chemical Biology - July 2, 2013 Category: Biochemistry Authors: Kamat SS, Raushel FM Tags: Curr Opin Chem Biol Source Type: research

Cyclotide biosynthesis.
Abstract Cyclotides are bioactive macrocyclic peptides from plants that are characterized by their exceptional stability and potential applications as protein engineering or drug design frameworks. Their stability arises from their unique cyclic cystine knot structure, which combines a head-to-tail cyclic peptide backbone with three conserved disulfide bonds having a knotted topology. Cyclotides are ribosomally synthesized by plants and expressed in a wide range of tissues, including leaves, flowers, stems and roots. Here we describe recent studies that have examined the biosynthesis of cyclotides and in particula...
Source: Current Opinion in Chemical Biology - June 25, 2013 Category: Biochemistry Authors: Craik DJ, Malik U Tags: Curr Opin Chem Biol Source Type: research

Biosynthetic machinery of ionophore polyether lasalocid: enzymatic construction of polyether skeleton.
Abstract Diversity of natural polycyclic polyethers originated from very simple yet versatile strategy consisting of epoxidation of linear polyene followed by epoxide opening cascade. To understand two-step enzymatic transformations at molecular basis, a flavin containing monooxygenase (EPX) Lsd18 and an epoxide hydrolase (EH) Lsd19 were selected as model enzymes for extensive investigation on substrate specificity, catalytic mechanism, cofactor requirement and crystal structure. This pioneering study on prototypical lasalocid EPX and EH provides insight into detailed mechanism of ionophore polyether assembly mach...
Source: Current Opinion in Chemical Biology - June 21, 2013 Category: Biochemistry Authors: Minami A, Oguri H, Watanabe K, Oikawa H Tags: Curr Opin Chem Biol Source Type: research

Target identification of biologically active small molecules via in situ methods.
Abstract The identification of potential cellular targets of small molecules is important in biomedical research and drug discovery, but has been challenging due to a lack of proteome-based methods that enable direct investigation of small molecule-protein interaction in live cells. This review summarizes some of the recent advances in target identification of bioactive molecules (including drugs and natural products) using in situ methods for cell-based proteome profiling of potential on and off targets. PMID: 23796909 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - June 21, 2013 Category: Biochemistry Authors: Su Y, Ge J, Zhu B, Zheng YG, Zhu Q, Yao SQ Tags: Curr Opin Chem Biol Source Type: research

Phosphorescence bioimaging using cyclometalated Ir(III) complexes.
Abstract Recent advances in the development of the phosphorescent Ir(III) complexes have made it possible to implement the phosphorescence modality in bioimaging applications. A variety of phosphorescent Ir(III) complexes have been synthesized and assessed in the context of in vitro and in vivo imaging, especially in subcellular organelle staining and the sensing of biologically important analytes. The examples presented here demonstrate that Ir(III) complexes provide attractive alternatives to fluorescent organic compounds in the construction of biolabels and biosensors. The complexes are particularly advantageou...
Source: Current Opinion in Chemical Biology - June 18, 2013 Category: Biochemistry Authors: You Y Tags: Curr Opin Chem Biol Source Type: research

Recent trends in analytical and structural glycobiology.
Abstract The great complexity of glycosylated biomolecules necessitates a set of powerful analytical methodologies to reveal functionally important structural features. Mass spectrometry (MS), with its different ionization techniques, mass analyzers, and detection strategies, has become the most important analytical method in glycomic and glycoproteomic investigations. In combination with MS, microscale separations (based on capillary chromatography and electrophoresis) and carbohydrate microchemistry, we feature here conceptually important applications of the recent years. This review focuses on methodological ad...
Source: Current Opinion in Chemical Biology - June 18, 2013 Category: Biochemistry Authors: Novotny MV, Alley WR Tags: Curr Opin Chem Biol Source Type: research

Quantitation of endogenous peptides using mass spectrometry based methods.
Abstract The mass spectrometry-based 'omics' sub-discipline that focuses on comprehensive, often exploratory, analyses of endogenous peptides involved in cell-to-cell communication is oftentimes referred to as peptidomics. Although the progress in bioanalytical technology development for peptide discovery has been tremendous, perhaps the largest advances have involved robust quantitative mass spectrometric approaches and data mining algorithms. These efforts have accelerated the discovery and validation of biomarkers, functionally important posttranslational modifications, and unexpected molecular interactions, in...
Source: Current Opinion in Chemical Biology - June 18, 2013 Category: Biochemistry Authors: Romanova EV, Dowd SE, Sweedler JV Tags: Curr Opin Chem Biol Source Type: research

Molecular imaging of live cells by Raman microscopy.
Abstract Raman microscopy represents an emerging class of tools for molecular imaging of live cells because of the rich information obtained by detecting molecular vibrations. Recently, several Raman imaging techniques based on the parallel detection of Raman spectra have been developed, which can achieve high spatial and temporal resolution suitable for live cell imaging. When combined with tiny Raman tags in the cellular silent region, Raman microscopy has capability to map the distribution of specific target small molecules with minimum perturbation from the tag. Here we review these recent advances in cell ima...
Source: Current Opinion in Chemical Biology - June 14, 2013 Category: Biochemistry Authors: Palonpon AF, Sodeoka M, Fujita K Tags: Curr Opin Chem Biol Source Type: research

Making connections-strategies for single molecule fluorescence biophysics.
Abstract Fluorescence spectroscopy and fluorescence microscopy carried out on the single molecule level are elegant methods to decipher complex biological systems; it can provide a wealth of information that frequently is obscured in the averaging of ensemble measurements. Fluorescence can be used to localise a molecule, study its binding with interaction partners and ligands, or to follow conformational changes in large multicomponent systems. Efficient labelling of proteins and nucleic acids is very important for any fluorescence method, and equally the development of novel fluorophores has been crucial in makin...
Source: Current Opinion in Chemical Biology - June 13, 2013 Category: Biochemistry Authors: Grohmann D, Werner F, Tinnefeld P Tags: Curr Opin Chem Biol Source Type: research

Synthetic fluorescent probes for monovalent copper.
Abstract Fluorescent probes are powerful and cost-effective tools for the detection of metal ions in biological systems. Compared to non-redox-active metal ions, the design of fluorescent probes for biological copper is challenging. Within the reducing cellular environment, copper is predominantly present in its monovalent oxidation state; therefore, the design of fluorescent probes for biological copper must take into account the rich redox and coordination chemistry of Cu(I). Recent progress in understanding the underlying solution chemistry and photophysical pathways led to the development of new probes that of...
Source: Current Opinion in Chemical Biology - June 13, 2013 Category: Biochemistry Authors: Fahrni CJ Tags: Curr Opin Chem Biol Source Type: research

Chemical tags: inspiration for advanced imaging techniques.
Abstract This review summarizes recent applications of chemical tags in conjunction with advanced bio-imaging techniques including single-molecule fluorescence, spatiotemporally resolved ensemble microscopy techniques, and imaging modalities beyond fluorescence. We aim to illustrate the unique advantages of chemical tags in facilitating contemporary microscopy to address biological problems that are difficult or near impossible to approach otherwise. We hope our review will inspire more innovative applications enabled by the mingling of these two growing fields. PMID: 23769339 [PubMed - as supplied by publish...
Source: Current Opinion in Chemical Biology - June 12, 2013 Category: Biochemistry Authors: Chen Z, Cornish VW, Min W Tags: Curr Opin Chem Biol Source Type: research

Protein labeling with fluorogenic probes for no-wash live-cell imaging of proteins.
Abstract Protein labeling by using a protein tag and its specific fluorescent probe is increasingly becoming a useful technique for the real-time imaging of proteins in living cells. Recently, fluorogenic probes for protein labeling were developed. When using these probes, a washing step is not required for the removal of free probes from the cells, thus, allowing rapid detection of proteins in living cells with high signal-to-noise ratio. Various chemical principles have been applied in the designing of probes to include a turn-on fluorescence switch that is activated by the protein labeling reaction. In this rev...
Source: Current Opinion in Chemical Biology - June 3, 2013 Category: Biochemistry Authors: Hori Y, Kikuchi K Tags: Curr Opin Chem Biol Source Type: research

Visualizing molecular diffusion through passive permeability barriers in cells: conventional and novel approaches.
Abstract Diffusion barriers are universal solutions for cells to achieve distinct organizations, compositions, and activities within a limited space. The influence of diffusion barriers on the spatiotemporal dynamics of signaling molecules often determines cellular physiology and functions. Over the years, the passive permeability barriers in various subcellular locales have been characterized using elaborate analytical techniques. In this review, we will summarize the current state of knowledge on the various passive permeability barriers present in mammalian cells. We will conclude with a description of several ...
Source: Current Opinion in Chemical Biology - May 31, 2013 Category: Biochemistry Authors: Lin YC, Phua SC, Lin B, Inoue T Tags: Curr Opin Chem Biol Source Type: research

Biofuels for the 21st century.
PMID: 23722079 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - May 27, 2013 Category: Biochemistry Authors: Burkart MD, Mayfield SP Tags: Curr Opin Chem Biol Source Type: research

Correctors of the basic trafficking defect of the mutant F508del-CFTR that causes cystic fibrosis.
Abstract Cystic fibrosis (CF) is the most frequent lethal genetic disease and the most frequent mutation is F508del-cystic fibrosis transmembrane regulator (CFTR). In common with some other protein trafficking diseases the mutant protein is functional but recognized by the cellular quality control system retained in the endoplasmic reticulum (ER) and degraded. There have been some recent impressive advances in developing corrector compounds that restore the trafficking of the mutant protein to the plasma membrane. The targets of these correctors and possible mechanisms of action are discussed. PMID: 23711435 ...
Source: Current Opinion in Chemical Biology - May 24, 2013 Category: Biochemistry Authors: Birault V, Solari R, Hanrahan J, Thomas DY Tags: Curr Opin Chem Biol Source Type: research

Fluorescent probes for monitoring regulated secretion.
Abstract Numerous secretory cells use the regulated secretory pathway to release signaling molecules. Regulated secretion is an essential component of the intercellular communication network of a multicellular organism and serves diverse functions in neurobiology, endocrinology, and many other aspects of animal physiology. Probes that can monitor a specific exocytotic event with high temporal and spatial resolution would be invaluable tools for studying the molecular and cellular mechanisms underlying stimulus-secretion coupling, and for characterizing secretion defects that are found in different human diseases. ...
Source: Current Opinion in Chemical Biology - May 24, 2013 Category: Biochemistry Authors: Li WH, Li D Tags: Curr Opin Chem Biol Source Type: research

Hydrothermal conversion of biomass to fuels and energetic materials.
Abstract Available biomass, preferentially residues, can be divided in two groups: biomass with a high or natural water content ('wet' or 'green' biomass) and biomass with low water content such as wood and straw. In 'dry' biomass gasification processes, originating in most coal processing technologies, biomass of low water content is necessary to avoid the energy loss by water evaporation. In contrast, hydrothermal processes need water as reaction medium; therefore, these processes are preferentially used for wet or 'green' biomass. In this review paper we will describe the main research directions in the hydroth...
Source: Current Opinion in Chemical Biology - May 23, 2013 Category: Biochemistry Authors: Kruse A, Funke A, Titirici MM Tags: Curr Opin Chem Biol Source Type: research

Advances in microalgae engineering and synthetic biology applications for biofuel production.
Abstract Among the technologies being examined to produce renewable fuels, microalgae are viewed by many in the scientific community as having the greatest potential to become economically viable. Algae are capable of producing greater than 50,000kg/acre/year of biomass [1]. Additionally, most algae naturally accumulate energy-dense oils that can easily be converted into transportation fuels. To reach economic parity with fossil fuels there are still several challenges. These include identifying crop protection strategies, improving harvesting and oil extraction processes, and increasing biomass productivity and o...
Source: Current Opinion in Chemical Biology - May 16, 2013 Category: Biochemistry Authors: Gimpel JA, Specht EA, Georgianna DR, Mayfield SP Tags: Curr Opin Chem Biol Source Type: research

Innovation in academic chemical screening: filling the gaps in chemical biology.
Abstract Academic screening centers across the world have endeavored to discover small molecules that can modulate biological systems. To increase the reach of functional-genomic and chemical screening programs, universities, research institutes, and governments have followed their industrial counterparts in adopting high-throughput paradigms. As academic screening efforts have steadily grown in scope and complexity, so have the ideas of what is possible with the union of technology and biology. This review addresses the recent conceptual and technological innovation that has been propelling academic screening int...
Source: Current Opinion in Chemical Biology - May 14, 2013 Category: Biochemistry Authors: Hasson SA, Inglese J Tags: Curr Opin Chem Biol Source Type: research

Two-in-One antibodies with dual action Fabs.
Abstract Mechanisms and biological roles of antibody multi-specificity are topics of high interest. Evidence of conformational flexibility in antigen-combining sites and their utility in the recognition of different antigens appeared two decades ago. In the last three years an appreciation has emerged that recognition of very much more diverse protein antigens is within the scope of multi-specificity and also that this is sometimes, but not always, associated with structural plasticity. The ability to invent non-promiscuous, high affinity antibodies which are 'specific' for more than one antigen such as the recent...
Source: Current Opinion in Chemical Biology - May 14, 2013 Category: Biochemistry Authors: Eigenbrot C, Fuh G Tags: Curr Opin Chem Biol Source Type: research

Engineering fatty acid biosynthesis in microalgae for sustainable biodiesel.
Abstract Microalgae are a promising feedstock for biodiesel and other liquid fuels due to their fast growth rate, high lipid yields, and ability to grow in a broad range of environments. However, many microalgae achieve maximal lipid yields only under stress conditions hindering growth and providing compositions not ideal for biofuel applications. Metabolic engineering of algal fatty acid biosynthesis promises to create strains capable of economically producing fungible and sustainable biofuels. The algal fatty acid biosynthetic pathway has been deduced by homology to bacterial and plant systems, and much of our u...
Source: Current Opinion in Chemical Biology - May 14, 2013 Category: Biochemistry Authors: Blatti JL, Michaud J, Burkart MD Tags: Curr Opin Chem Biol Source Type: research

Inhibitors of BACE for treating Alzheimer's disease: a fragment-based drug discovery story.
Abstract Several fragment-based methods have been applied to the discovery of new lead sources for inhibitors of BACE1, an important therapeutic target for Alzheimer's disease. Among the most common fragment hits were various amidine-containing molecules in which the amidine engaged in discrete H-bond donor-acceptor interaction with the BACE1 catalytic dyad. Structure and medicinal chemistry knowledge-based optimization with emphasis on ligand efficiency resulted in identification of a key pharmacophore comprising a non-planar cyclic amidine scaffold directly attached to a phenyl group projecting into S1. This key...
Source: Current Opinion in Chemical Biology - May 14, 2013 Category: Biochemistry Authors: Stamford A, Strickland C Tags: Curr Opin Chem Biol Source Type: research

Next generation therapeutics.
PMID: 23683350 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - May 14, 2013 Category: Biochemistry Authors: Carter PJ, Hazuda D, Wells JA Tags: Curr Opin Chem Biol Source Type: research

The human microbiome is a source of therapeutic drug targets.
Abstract It was appreciated early in drug discovery that the microbiota play an important role in the efficacy of therapeutic compounds. Indeed, the first antibiotic sulfa drugs were shown in the 1940s to be transformed by the bacteria that encode what we now call the intestinal microbiome. Here we briefly review the roles symbiotic bacteria play in the chemistry of human health, and we focus on the emerging appreciation that specific enzyme targets expressed by microbial symbiotes can be selectively disrupted to achieve clinical outcomes. We conclude that components of the microbiome should be considered 'druggab...
Source: Current Opinion in Chemical Biology - May 13, 2013 Category: Biochemistry Authors: Wallace BD, Redinbo MR Tags: Curr Opin Chem Biol Source Type: research

Chemistry and combustion of fit-for-purpose biofuels.
Abstract From the inception of internal combustion engines, biologically derived fuels (biofuels) have played a role. Nicolaus Otto ran a predecessor to today's spark-ignition engine with an ethanol fuel blend in 1860. At the 1900 Paris world's fair, Rudolf Diesel ran his engine on peanut oil. Over 100 years of petroleum production has led to consistency and reliability of engines that demand standardized fuels. New biofuels can displace petroleum-based fuels and produce positive impacts on the environment, the economy, and the use of local energy sources. This review discusses the combustion, performance and othe...
Source: Current Opinion in Chemical Biology - May 8, 2013 Category: Biochemistry Authors: Rothamer DA, Donohue TJ Tags: Curr Opin Chem Biol Source Type: research

Protein conjugation with genetically encoded unnatural amino acids.
Abstract The site-specific incorporation of unnatural amino acids with orthogonal chemical reactivity into proteins enables the synthesis of structurally defined protein conjugates. Amino acids containing ketone, azide, alkyne, alkene, and tetrazine side chains can be genetically encoded in response to nonsense and frameshift codons. These bio-orthogonal chemical handles allow precise control over the site and stoichiometry of conjugation, and have enabled medicinal chemistry-like optimization of the physical and biological properties of protein conjugates, especially the next-generation protein therapeutics. ...
Source: Current Opinion in Chemical Biology - May 8, 2013 Category: Biochemistry Authors: Kim CH, Axup JY, Schultz PG Tags: Curr Opin Chem Biol Source Type: research

Production of advanced biofuels in engineered E. coli.
Abstract Commercial fermentation processes have long taken advantage of the synthetic power of living systems to rapidly and efficiently transform simple carbon sources into complex molecules. In this regard, the ability of yeasts to produce ethanol from glucose at exceptionally high yields has served as a key feature in its use as a fuel, but is also limited by the poor molecular properties of ethanol as a fuel such as high water miscibility and low energy density. Advances in metabolic engineering and synthetic biology allow us to begin constructing new high-flux pathways for production of next generation biofue...
Source: Current Opinion in Chemical Biology - May 6, 2013 Category: Biochemistry Authors: Wen M, Bond-Watts BB, Chang MC Tags: Curr Opin Chem Biol Source Type: research

Allosteric inhibition of HIV-1 integrase activity.
Abstract HIV-1 integrase is an important therapeutic target in the fight against HIV/AIDS. Integrase strand transfer inhibitors (INSTIs), which target the enzyme active site, have witnessed clinical success over the past 5 years, but the generation of drug resistance poses challenges to INSTI-based therapies moving forward. Integrase is a dynamic protein, and its ordered multimerization is critical to enzyme activity. The integrase tetramer, bound to viral DNA, interacts with host LEDGF/p75 protein to tether integration to active genes. Allosteric integrase inhibitors (ALLINIs) that compete with LEDGF/p75 for bind...
Source: Current Opinion in Chemical Biology - May 3, 2013 Category: Biochemistry Authors: Engelman A, Kessl JJ, Kvaratskhelia M Tags: Curr Opin Chem Biol Source Type: research

Targeting the untargetable: recent advances in the selective chemical modulation of protein phosphatase-1 activity.
n M Abstract Protein phosphatase-1 (PP1) has long been neglected as a potential drug target owing to its misinterpreted unselective nature. However, growing evidence demonstrates that PP1 is highly selective in complex with regulatory proteins at the holoenzyme level, each of which is involved in different essential cellular signaling events. Here we summarize promising approaches to specifically activate or inhibit PP1 activity, and discuss remaining challenges and potential solutions. The summarized chemical tools pave the way for a better understanding of PP1's role in signaling networks, and the effects result...
Source: Current Opinion in Chemical Biology - May 3, 2013 Category: Biochemistry Authors: Chatterjee J, Köhn M Tags: Curr Opin Chem Biol Source Type: research

Targeting unfolded protein response signaling pathways to ameliorate protein misfolding diseases.
Abstract Protein homeostasis (or proteostasis) within the endoplasmic reticulum (ER) is regulated by the unfolded protein response (UPR). The UPR consists of three integrated signaling pathways activated by the accumulation of misfolded proteins within the ER lumen. Activation of the UPR alters ER proteostasis through translational attenuation of new protein synthesis and transcriptional remodeling of ER proteostasis pathways, providing a mechanism to adapt ER proteostasis in response to cellular stress. The capacity of the UPR to alter ER proteostasis suggests that exogenous manipulation of UPR signaling pathways...
Source: Current Opinion in Chemical Biology - May 3, 2013 Category: Biochemistry Authors: Ryno LM, Wiseman RL, Kelly JW Tags: Curr Opin Chem Biol Source Type: research

Stabilizing membrane proteins through protein engineering.
n A Abstract Integral membrane proteins (IMPs) are crucial components of all cells but are difficult to study in vitro because they are generally unstable when removed from their native membranes using detergents. Despite the major biomedical relevance of IMPs, less than 1% of Protein Data Bank (PDB) entries are IMP structures, reflecting the technical gap between studies of soluble proteins compared to IMPs. Stability can be engineered into IMPs by inserting stabilizing mutations, thereby generating proteins that can be successfully applied to biochemical and structural studies when solubilized in detergent micel...
Source: Current Opinion in Chemical Biology - April 29, 2013 Category: Biochemistry Authors: Scott DJ, Kummer L, Tremmel D, Plückthun A Tags: Curr Opin Chem Biol Source Type: research

Advanced biofuel production by the yeast Saccharomyces cerevisiae.
Abstract Replacement of conventional transportation fuels with biofuels will require production of compounds that can cover the complete fuel spectrum, ranging from gasoline to kerosene. Advanced biofuels are expected to play an important role in replacing fossil fuels because they have improved properties compared with ethanol and some of these may have the energy density required for use in heavy duty vehicles, ships, and aviation. Moreover, advanced biofuels can be used as drop-in fuels in existing internal combustion engines. The yeast cell factory Saccharomyces cerevisiae can be turned into a producer of high...
Source: Current Opinion in Chemical Biology - April 26, 2013 Category: Biochemistry Authors: Buijs NA, Siewers V, Nielsen J Tags: Curr Opin Chem Biol Source Type: research

Targeting T cells to tumor cells using bispecific antibodies.
Abstract The immune system, and in particular T cells, can be harnessed to treat cancer. Several bispecific T cell engaging antibodies of the BiTE(®) format are in early or late-stage clinical development. These small recombinant antibody constructs effectively trigger killing of cancer cells by temporarily attached, polyclonal T cells. Blinatumomab, a CD19/CD3-bispecific BiTE(®) antibody, has demonstrated high clinical activity in B cell leukemia and lymphoma patients. Three additional BiTE antibodies directed against surface target antigen expressed on solid tumors are being evaluated in phase I clinical...
Source: Current Opinion in Chemical Biology - April 25, 2013 Category: Biochemistry Authors: Frankel SR, Baeuerle PA Tags: Curr Opin Chem Biol Source Type: research