Recent progress in chemical synthesis of bacterial surface glycans.
Abstract With the continuing advancement of carbohydrate chemical synthesis, bacterial glycomes have become increasingly attractive and accessible synthetic targets. Although bacteria also produce carbohydrate-containing secondary metabolites, our review here will cover recent chemical synthetic efforts on bacterial surface glycans. The obtained compounds are excellent candidates for the development of improved structurally defined glycoconjugate vaccines to combat bacterial infections. They are also important probes for investigating glycan-protein interactions. Glycosylation strategies applied for the formation ...
Source: Current Opinion in Chemical Biology - September 10, 2020 Category: Biochemistry Authors: Li R, Yu H, Chen X Tags: Curr Opin Chem Biol Source Type: research

Increasing the chemical space of proteins in living cells via genetic code expansion.
Abstract In recent years it has become possible to genetically encode an expanded set of designer amino acids with tailored chemical and physical properties (dubbed unnatural amino acids, UAAs) into proteins in living cells by expanding the genetic code. Together with developments in chemistries that are amenable to and selective within physiological settings, these strategies have started to have a big impact on biological studies, as they enable exciting in cellulo applications. Here we highlight recent advances to covalently stabilize transient protein-protein interactions and capture enzyme substrate-complexes...
Source: Current Opinion in Chemical Biology - September 7, 2020 Category: Biochemistry Authors: Krauskopf K, Lang K Tags: Curr Opin Chem Biol Source Type: research

tRNA-dependent amide bond-forming enzymes in peptide natural product biosynthesis.
Abstract In the ribosome-independent biosynthesis of peptide natural products, amino acid building blocks are generally activated in the form of phosphoesters, esters, or thioesters prior to amide bond formation. Following the recent discovery of bacterial enzymes that utilize an aminoacyl ester with a transfer ribonucleic acid (tRNA) in primary metabolism, the number of tRNA-dependent enzymes used in biosynthetic studies of peptide natural products has increased steadily. In this review, we summarize the rapidly growing knowledge base regarding two types of tRNA-dependent enzymes, which are structurally and funct...
Source: Current Opinion in Chemical Biology - September 5, 2020 Category: Biochemistry Authors: Maruyama C, Hamano Y Tags: Curr Opin Chem Biol Source Type: research

Unremitting progresses for phosphoprotein synthesis.
Abstract Phosphorylation, one of the important protein post-translational modifications, is involved in many essential cellular processes. Site-specifical and homogeneous phosphoproteins can be used as probes for elucidating the protein phosphorylation network and as potential therapeutics for interfering their involved biological events. However, the generation of phosphoproteins has been challenging owing to the limitation of chemical synthesis and protein expression systems. Despite the pioneering discoveries in phosphoprotein synthesis, over the past decade, great progresses in this field have also been made t...
Source: Current Opinion in Chemical Biology - September 1, 2020 Category: Biochemistry Authors: Duan HZ, Nie ZK, Li Y, Chen YX Tags: Curr Opin Chem Biol Source Type: research

A critical evaluation of probes for cysteine sulfenic acid.
Abstract Cysteine oxidation is important in cellular redox regulation, signaling, and biocatalysis. To understand the biological relevance of cysteine oxidation, it is desirable to identify the proteins involved, the site of the oxidized cysteine, and the relevant oxidation states. Because the thiol of cysteine can be converted to a wide range of oxidation states, mapping these oxidative modifications is challenging. The dynamic and reversible nature of many cysteine oxidation states compounds the difficulty in such proteomic analyses. In this review, we examine methods to detect cysteine sulfenic acid - a pa...
Source: Current Opinion in Chemical Biology - August 28, 2020 Category: Biochemistry Authors: Pople JMM, Chalker JM Tags: Curr Opin Chem Biol Source Type: research

Natural product discovery through microbial genome mining.
Abstract The advent of the genomic era has opened up enormous possibilities for the discovery of new natural products. Also known as specialized metabolites, these compounds produced by bacteria, fungi, and plants have long been sought for their bioactive properties. Innovations in both DNA sequencing technologies and bioinformatics now allow the wealth of sequence data to be mined at both the genome and metagenome levels for new specialized metabolites. However, a key problem that remains is rapidly and efficiently linking these identified genes to their corresponding compounds. Within this review, we provide spe...
Source: Current Opinion in Chemical Biology - August 24, 2020 Category: Biochemistry Authors: Kenshole E, Herisse M, Michael M, Pidot SJ Tags: Curr Opin Chem Biol Source Type: research

Anatomy of a crosslinker.
Abstract Crosslinking mass spectrometry has become a core technology in structural biology and is expanding its reach towards systems biology. Its appeal lies in a rapid workflow, high sensitivity and the ability to provide data on proteins in complex systems, even in whole cells. The technology depends heavily on crosslinking reagents. The anatomy of crosslinkers can be modular, sometimes comprising combinations of functional groups. These groups are defined by concepts including: reaction selectivity to increase information density, enrichability to improve detection, cleavability to enhance the identification p...
Source: Current Opinion in Chemical Biology - August 20, 2020 Category: Biochemistry Authors: Belsom A, Rappsilber J Tags: Curr Opin Chem Biol Source Type: research

Imaging mRNA trafficking in living cells using fluorogenic proteins.
Abstract mRNAs play key roles in regulating diverse cellular functions. In many cases, mRNAs exhibit distinct intracellular localizations that are necessary for the spatiotemporal control of protein expression in cells. Therefore, imaging the localization and dynamics of these mRNAs is crucial for understanding diverse aspects of cellular function. In this review, we summarize how mRNA imaging can be achieved using tethered fluorescent proteins and fluorogenic aptamers. We discuss 'fluorogenic proteins' and describe how these recently developed RNA-regulated fluorescent proteins simplify mRNA imaging experiments. ...
Source: Current Opinion in Chemical Biology - August 20, 2020 Category: Biochemistry Authors: Wu J, Jaffrey SR Tags: Curr Opin Chem Biol Source Type: research

Editorial overview: Molecular imaging.
PMID: 32826170 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - August 18, 2020 Category: Biochemistry Authors: Palmer AE, C Hammond M Tags: Curr Opin Chem Biol Source Type: research

Imaging voltage and brain chemistry with genetically encoded sensors and modulators.
Abstract Neurons and glia are functionally organized into circuits and higher-order structures that allow the precise information processing required for complex behaviors. To better understand the structure and function of the brain, we must understand synaptic connectivity, action potential generation and propagation, as well as well-orchestrated molecular signaling. Recently, dramatically improved sensors for voltage, intracellular calcium, and neurotransmitters/modulators, combined with advanced microscopy provide new opportunities for in vivo dissection of cellular and circuit activity in awake, behaving...
Source: Current Opinion in Chemical Biology - August 18, 2020 Category: Biochemistry Authors: Pal A, Tian L Tags: Curr Opin Chem Biol Source Type: research

How synthetic biology can help bioremediation.
Abstract The World Health Organization reported that "an estimated 12.6 million people died as a result of living or working in an unhealthy environment in 2012, nearly 1 in 4 of total global deaths". Air, water and soil pollution were the significant risk factors, and there is an urgent need for effective remediation strategies. But tackling this problem is not easy; there are many different types of pollutants, often widely dispersed, difficult to locate and identify, and in many cases cost-effective clean-up techniques are lacking. Biology offers enormous potential as a tool to develop microbial&...
Source: Current Opinion in Chemical Biology - August 14, 2020 Category: Biochemistry Authors: Rylott EL, Bruce NC Tags: Curr Opin Chem Biol Source Type: research

Enzyme-targeted fluorescent small-molecule probes for bacterial imaging.
Abstract Molecular imaging methods to visualize myriad biochemical processes in bacteria have traditionally been dependent upon molecular biology techniques to incorporate fluorescent biomolecules (e.g., fusion proteins). Such methods have been instrumental in our understanding of how bacteria function but are not without drawbacks, including potential perturbation to native protein expression and function. To overcome these limitations, the use of fluorescent small-molecule probes has gained much attention. Here, we highlight examples from the recent literature that showcase the utility of small-molecule probes f...
Source: Current Opinion in Chemical Biology - August 13, 2020 Category: Biochemistry Authors: Marshall AP, Shirley JD, Carlson EE Tags: Curr Opin Chem Biol Source Type: research

Editorial overview: Epigenetics equals chemical biology.
PMID: 32800628 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - August 13, 2020 Category: Biochemistry Authors: Kawamura A, Ganesan A Tags: Curr Opin Chem Biol Source Type: research

The evolving capabilities of enzyme-mediated proximity labeling.
Abstract The subcellular organization of proteins and RNA molecules is crucial for their proper functions. Over the past decade, both ligase-mediated and peroxidase-mediated proximity labeling (PL) techniques have been developed to map biomolecules at near-nanometer spatial resolution and subminute temporal resolution. These methods are shedding light on the spatial arrangement of proteome and transcriptome in their native context. Here, we review the recent evolution and applications of PL techniques, compare and contrast the two classes of methods, and highlight emerging trends and future opportunities. PMI...
Source: Current Opinion in Chemical Biology - August 12, 2020 Category: Biochemistry Authors: Zhou Y, Zou P Tags: Curr Opin Chem Biol Source Type: research

Two-hit wonders: The expanding universe of multitargeting epigenetic agents.
Abstract Multitargeting involves the application of molecules that are deliberately intended to bind to two or more unrelated cellular targets with high affinity. In epigenetic chemical biology and drug discovery, the rational design of multitargeting agents has evolved to a sophisticated level, and there are now five examples that have reached clinical trials. This review covers recent developments in the field and future prospects. PMID: 32784072 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - August 9, 2020 Category: Biochemistry Authors: de Lera AR, Ganesan A Tags: Curr Opin Chem Biol Source Type: research

All-atom simulations to studying metallodrugs/target interactions.
ato A Abstract Metallodrugs are extensively used to treat and diagnose distinct disease types. The unique physical-chemical properties of metal ions offer tantalizing opportunities to tailor effective scaffolds for selectively targeting specific biomolecules. Modern experimental techniques have collected a large body of structural data concerning the interactions of metallodrugs with their biomolecular targets, although being unable to exhaustively assess the molecular basis of their mechanism of action. In this scenario, the complementary use of accurate computational methods allows uncovering the minutiae of met...
Source: Current Opinion in Chemical Biology - August 8, 2020 Category: Biochemistry Authors: Janoš P, Spinello A, Magistrato A Tags: Curr Opin Chem Biol Source Type: research

Expanding the applicability of cytochrome P450s and other haemoproteins.
Abstract Cytochrome P450BM3 has long been regarded as a promising candidate for use as a biocatalyst, owing to its excellent efficiency for the hydroxylation of unactivated C-H bonds. However, owing because of its high substrate specificity, its possible applications have been severely limited. Consequently, various approaches have been proposed to overcome the enzyme's natural limitations, thereby expanding its substrate scope to encompass non-native substrates, evoking chemoselectivity, regioselectivity and stereoselectivity and enabling previously inaccessible chemical conversions. Herein, these approaches will...
Source: Current Opinion in Chemical Biology - August 8, 2020 Category: Biochemistry Authors: Ariyasu S, Stanfield JK, Aiba Y, Shoji O Tags: Curr Opin Chem Biol Source Type: research

Revealing the functional roles of tyrosine sulfation using synthetic sulfopeptides and sulfoproteins.
Abstract The decoration of proteins with post-translational modifications (PTMs) serves as a mechanism to expand the functional repertoire of the proteome. Tyrosine sulfation is a PTM that has been shown to be a key regulator of extracellular protein-protein interactions in a select number of examples. However, the challenges associated with identifying and characterising the functional consequences of tyrosine sulfation have hindered our ability to understand the full scope of its role in the wider proteome when compared with that of other PTMs, for example, phosphorylation and glycosylation. In this account, we ...
Source: Current Opinion in Chemical Biology - August 7, 2020 Category: Biochemistry Authors: Maxwell JWC, Payne RJ Tags: Curr Opin Chem Biol Source Type: research

Isocitrate dehydrogenase variants in cancer - Cellular consequences and therapeutic opportunities.
Abstract Abnormal metabolism is common in cancer cells and often correlates with mutations in genes encoding for enzymes involved in small-molecule metabolism. Isocitrate dehydrogenase 1 (IDH1) is the most frequently mutated metabolic gene in cancer. Cancer-associated substitutions in IDH1 and IDH2 impair wild-type production of 2-oxoglutarate and reduced nicotinamide adenine dinucleotide phosphate (NADPH) from isocitrate and oxidised nicotinamide adenine dinucleotide phosphate (NADP+ ), and substantially promote the IDH variant catalysed conversion of 2-oxoglutarate to d-2-hydroxyglutarate (d-2HG). Elevated ...
Source: Current Opinion in Chemical Biology - August 7, 2020 Category: Biochemistry Authors: Liu S, Cadoux-Hudson T, Schofield CJ Tags: Curr Opin Chem Biol Source Type: research

Sequencing enabling design and learning in synthetic biology.
Abstract The ability to read and quantify nucleic acids such as DNA and RNA using sequencing technologies has revolutionized our understanding of life. With the emergence of synthetic biology, these tools are now being put to work in new ways - enabling de novo biological design. Here, we show how sequencing is supporting the creation of a new wave of biological parts and systems, as well as providing the vast data sets needed for the machine learning of design rules for predictive bioengineering. However, we believe this is only the tip of the iceberg and end by providing an outlook on recent advances that will l...
Source: Current Opinion in Chemical Biology - August 6, 2020 Category: Biochemistry Authors: Gilliot PA, Gorochowski TE Tags: Curr Opin Chem Biol Source Type: research

Enzyme evolution in natural products biosynthesis: target- or diversity-oriented?
Abstract Natural product biosynthesis (NPB) is the Panda's Thumb of evolutionary biochemistry. Arm races between organisms, and ever-changing environments, result in relentless innovation. This review focusses on enzyme evolution in NPB. First, we review cases of de novo emergence, whereby a completely new enzymatic activity arose in a ligand-binding protein, or a new enzyme emerged including a completely new scaffold. Second, we briefly review the current models for enzyme evolution, and how they explain the inherent promiscuity of NPB enzymes and their tendency to produce multiple related products. We thus sugge...
Source: Current Opinion in Chemical Biology - August 6, 2020 Category: Biochemistry Authors: Noda-Garcia L, Tawfik DS Tags: Curr Opin Chem Biol Source Type: research

Designer metalloenzymes for synthetic biology: Enzyme hybrids for catalysis.
This report will briefly review recent advances in artificial metalloenzyme design, followed by summarising recent studies that have looked at the use of these hybrid catalysts in vivo and in enzymatic cascades, therefore exploring their potential for synthetic biology. PMID: 32768658 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - August 5, 2020 Category: Biochemistry Authors: Jarvis AG Tags: Curr Opin Chem Biol Source Type: research

Protein engineering for selective proteomics.
Abstract Post-translational modifications, complex formation, subcellular localization, and cell-type-specific expression create functionally distinct protein subpopulations that enable living systems to execute rapid and precise responses to changing conditions. Systems-level analysis of these subproteomes remains challenging, requiring preservation of spatial information or enrichment of species that are transient and present at low abundance. Engineered proteins have emerged as important tools for selective proteomics based on their capacity for highly specific molecular recognition and their genetic targetabil...
Source: Current Opinion in Chemical Biology - August 5, 2020 Category: Biochemistry Authors: Radziwon K, Weeks AM Tags: Curr Opin Chem Biol Source Type: research

Activity- and reactivity-based proteomics: Recent technological advances and applications in drug discovery.
Abstract Activity-based protein profiling (ABPP) is recognized as a powerful and versatile chemoproteomic technology in drug discovery. Central to ABPP is the use of activity-based probes to report the activity of specific enzymes or reactivity of amino acid types in complex biological systems. Over the last two decades, ABPP has facilitated the identification of new drug targets and discovery of lead compounds in human and infectious disease. Furthermore, as part of a sustained global effort to illuminate the druggable proteome, the repertoire of target classes addressable with activity-based probes has vastly ex...
Source: Current Opinion in Chemical Biology - August 5, 2020 Category: Biochemistry Authors: Benns HJ, Wincott CJ, Tate EW, Child MA Tags: Curr Opin Chem Biol Source Type: research

Potential-dependent extracellular electron transfer pathways of exoelectrogens.
Abstract Exoelectrogens are distinct from other bacteria owing to their unique extracellular electron transfer (EET) abilities that allow for anaerobic respiration with various external redox-active surfaces, including electrode and metal oxides. Although the EET process is known to trigger diverse extracellular redox reactions, the reverse impact has been long overlooked. Recent evidences show that exoelectrogens can sense the potential changes of external surfaces and alter their EET strategies accordingly, which imparts them remarkable abilities in adapting to diverse and redox-variable environment. This mini-r...
Source: Current Opinion in Chemical Biology - August 5, 2020 Category: Biochemistry Authors: Liu DF, Li WW Tags: Curr Opin Chem Biol Source Type: research

Acoustic-based chemical tools for profiling the tumor microenvironment.
Abstract Acoustic-based imaging modalities (e.g. ultrasonography and photoacoustic imaging) have emerged as powerful approaches to noninvasively visualize the interior of the body due to their biocompatibility and the ease of sound transmission in tissue. These technologies have recently been augmented with an array of chemical tools that enable the study and modulation of the tumor microenvironment at the molecular level. In addition, the application of ultrasound and ultrasound-responsive materials has been used for drug delivery with high spatiotemporal control. In this review, we highlight recent advances...
Source: Current Opinion in Chemical Biology - August 5, 2020 Category: Biochemistry Authors: Yadav AK, Hernandez S, Su S, Chan J Tags: Curr Opin Chem Biol Source Type: research

Synthetic biology enabling access to designer polyketides.
Abstract The full potential of polyketide discovery has yet to be reached owing to a lack of suitable technologies and knowledge required to advance engineering of polyketide biosynthesis. Recent investigations on the discovery, enhancement, and non-natural use of these biosynthetic gene clusters via computational biology, metabolic engineering, structural biology, and enzymology-guided approaches have facilitated improved access to designer polyketides. Here, we discuss recent successes in gene cluster discovery, host strain engineering, precursor-directed biosynthesis, combinatorial biosynthesis, polyketide tail...
Source: Current Opinion in Chemical Biology - August 3, 2020 Category: Biochemistry Authors: Malico AA, Nichols L, Williams GJ Tags: Curr Opin Chem Biol Source Type: research

Domain cross-talk in regulation of histone modifications: Molecular mechanisms and targeting opportunities.
Abstract Functional cross-talk between the catalytic and reader domains in chromatin-modifying enzymes and protein complexes enable coordinated regulation of chromatin modification status, and consequently impacts chromatin-associated processes. ZZ domains are a recently identified class of chromatin readers that recognize the N-terminal region of histone H3 to direct and regulate acetylation activity of several histone acetylation complexes. Cross-talk between chromatin readers sensitive to methylation, and catalytic domains of methyltransferases and demethylases impacts substrate specificity, catalytic activity,...
Source: Current Opinion in Chemical Biology - August 3, 2020 Category: Biochemistry Authors: Longbotham JE, Zhang MY, Fujimori DG Tags: Curr Opin Chem Biol Source Type: research

Toward  enhanced performance of integrated photo-bioelectrochemical systems: Taxa and functions in bacteria-algae communities.
Toward enhanced performance of integrated photo-bioelectrochemical systems: Taxa and functions in bacteria-algae communities. Curr Opin Chem Biol. 2020 Aug 01;59:130-139 Authors: Wang Z, He Z, Young EB Abstract An integrated photo-bioelectrochemical (IPB) system uses microalgae in the cathode of a microbial fuel cell to achieve higher electricity generation and nutrient removal from wastewater. Using multivariate analysis and surveys of IPB studies, this paper identifies key algal and bacterial taxa and discusses their functions critical for IPB performance. Unicellular algae with high photosynth...
Source: Current Opinion in Chemical Biology - August 1, 2020 Category: Biochemistry Authors: Wang Z, He Z, Young EB Tags: Curr Opin Chem Biol Source Type: research

Shewanella biofilm development and engineering for environmental and bioenergy applications.
Abstract The genus Shewanella comprises about 70 species of Gram-negative, facultative anaerobic bacteria inhabiting various environments, which have shown great potential in various biotechnological applications ranging from environmental bioremediation, metal(loid) recovery and material synthesis to bioenergy generation. Most environmental and energy applications of Shewanella involve the biofilm mode of growth on surfaces of solid minerals or electrodes. In this article, we first provide an overview of Shewanella biofilm biology with the focus on biofilm dynamics, biofilm matrix, and key signalling systems...
Source: Current Opinion in Chemical Biology - August 1, 2020 Category: Biochemistry Authors: Mukherjee M, Zaiden N, Teng A, Hu Y, Cao B Tags: Curr Opin Chem Biol Source Type: research

Enhancing native chemical ligation for challenging chemical protein syntheses.
Abstract Native chemical ligation has enabled the chemical synthesis of proteins for a wide variety of applications (e.g., mirror-image proteins). However, inefficiencies of this chemoselective ligation in the context of large or otherwise challenging protein targets can limit the practical scope of chemical protein synthesis. In this review, we focus on recent developments aimed at enhancing and expanding native chemical ligation for challenging protein syntheses. Chemical auxiliaries, use of selenium chemistry, and templating all enable ligations at otherwise suboptimal junctions. The continuing development of t...
Source: Current Opinion in Chemical Biology - July 31, 2020 Category: Biochemistry Authors: Giesler RJ, Erickson PW, Kay MS Tags: Curr Opin Chem Biol Source Type: research

Targeting epigenetic reader domains by chemical biology.
Abstract Over the past years, growing interest toward post-translational modifications (PTMs) of histones and nonhistone proteins has prompted academia and industrial research groups to develop different approaches to better understand the link between PTMs and pathological states. Selective recognition of PTMs is carried out by reader modules, which mediate the biological readout of epigenetic mechanisms. Progress in medicinal chemistry and chemical biology has contributed to corroborate the role of reader domains in chromatin-binding proteins as potential therapeutic targets. Here, we review the state-of-the-art...
Source: Current Opinion in Chemical Biology - July 30, 2020 Category: Biochemistry Authors: Cipriano A, Sbardella G, Ciulli A Tags: Curr Opin Chem Biol Source Type: research

Biosynthesis of marine toxins.
Abstract Throughout history, humans have encountered natural toxic chemicals from the ocean environment, often through contaminated seafood. Although marine toxins can be harmful to human health and devastate local environments when they are produced during algal bloom events, they are also important biochemical research reagents and drug leads in medicine. In spite of their long history, the biosynthetic origin of many well-known marine toxins has remained elusive. New biosynthetic insights have shed light on the chemical transformations that create the complex structures of several iconic oceanic toxins. To that...
Source: Current Opinion in Chemical Biology - July 27, 2020 Category: Biochemistry Authors: Chekan JR, Fallon TR, Moore BS Tags: Curr Opin Chem Biol Source Type: research

Biogenesis of the peptide-derived redox cofactor pyrroloquinoline quinone.
Abstract Pyrroloquinoline quinone (PQQ) is a peptide-derived redox cofactor produced by prokaryotes that also plays beneficial roles in organisms from other kingdoms. We review recent developments on the pathway of PQQ biogenesis, focusing on the mechanisms of PqqE, PqqF/G, and PqqB. These advances may shed light on other, uncharacterized biosynthetic pathways. PMID: 32731194 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - July 27, 2020 Category: Biochemistry Authors: Zhu W, Klinman JP Tags: Curr Opin Chem Biol Source Type: research

The catalytic mechanism of sulfoxide synthases.
Abstract Sulfoxide synthases are non-heme iron enzymes that catalyze oxidative carbonsulfur bond formation in the biosynthesis of thiohistidines such as ergothioneine and ovothiol. The catalytic mechanism of these enzymes has been studied by protein crystallography, steady-state kinetics, non-natural amino acid incorporation and computational modeling. This review discusses the current status of this research and also highlights similarities between the CS bond forming activity of sulfoxide synthases with that of synthetic coordination compounds. PMID: 32726707 [PubMed - as supplied by publisher] (Source: Cur...
Source: Current Opinion in Chemical Biology - July 26, 2020 Category: Biochemistry Authors: Stampfli AR, Seebeck FP Tags: Curr Opin Chem Biol Source Type: research

Molecular mechanisms of microbial transmembrane electron transfer of electrochemically active bacteria.
Abstract Electrochemically active bacteria (EAB) can release electrons generated by anaerobic respiration to various electron acceptors in various bioelectrochemical systems via transmembrane electron transfer (TET). This renders EAB an important application in terms of energy generation. In this review, recent progress in research toward the TET process of EAB is outlined. Differences in TET process between Gram-positive and Gram-negative EAB are analyzed from a cellular structure perspective to comprehensively understand the molecular mechanism involved in TET. In addition, possible avenues for increasing TET ef...
Source: Current Opinion in Chemical Biology - July 23, 2020 Category: Biochemistry Authors: Xiao X, Yu HQ Tags: Curr Opin Chem Biol Source Type: research

Photocaged functional nucleic acids for spatiotemporal imaging in biology.
Abstract Imaging of species in living organisms with high spatiotemporal resolution is essential for understanding biological processes. While functional nucleic acids (FNAs), such as catalytic nucleic acids and aptamers, have emerged as effective sensors for a wide range of molecules, photocaged control of these FNAs has played a key role in translating them into bioimaging agents with high spatiotemporal control. In this review, we summarize methods and results of photocaged FNAs based on photolabile modifications, photoisomerization, and photothermal activation. Future directions, including strategies to improv...
Source: Current Opinion in Chemical Biology - July 8, 2020 Category: Biochemistry Authors: Wu Y, Yang Z, Lu Y Tags: Curr Opin Chem Biol Source Type: research

Recent advances of thiol-selective bioconjugation reactions.
Abstract Proteins are the most abundant biomolecules within a cell and are involved in all biochemical cellular processes, fulfilling specific functions with unmatched precision. This unique specificity makes proteins an ideal scaffold to generate tools for the exploration of natural systems or for the construction of modern therapeutics. Thus, the chemoselective modification of proteins with functionalities that are not defined by the genetic code has become an indispensable approach for life science research and the development of therapeutics. Amongst site-selective strategies for protein modification, cysteine...
Source: Current Opinion in Chemical Biology - July 6, 2020 Category: Biochemistry Authors: Ochtrop P, Hackenberger CPR Tags: Curr Opin Chem Biol Source Type: research

Mechanosensitive channels of Corynebacterium glutamicum functioning as exporters of l-glutamate and other valuable metabolites.
Abstract In the industrial l-glutamate production established on the use of Corynebacterium glutamicum, l-glutamate synthesized intracellularly is exported through mechanosensitive transmembrane channel proteins (MscCG and MscCG2) activated by the force-from-lipids. The involvement of MscCG2 in l-glutamate export by C. glutamicum was demonstrated in 2018; however, MscCG was previously found to be the major exporter of l-glutamate. Recent advances in research methods, such as development of the microbial patch clamp, revealed unique characteristics of MscCG, including its conductance, opening and closing thresholds...
Source: Current Opinion in Chemical Biology - July 6, 2020 Category: Biochemistry Authors: Kawasaki H, Martinac B Tags: Curr Opin Chem Biol Source Type: research

Advances of epigenetic editing.
Abstract Epigenetic editing refers to the locus-specific targeting of epigenetic enzymes to rewrite the local epigenetic landscape of an endogenous genomic site, often with the aim of transcriptional reprogramming. Implementing clustered regularly interspaced short palindromic repeat-dCas9 greatly accelerated the advancement of epigenetic editing, yielding preclinical therapeutic successes using a variety of epigenetic enzymes. ,CRISPR/dCas9 Here, were review the current applications of these epigenetic editing tools in mammalians and shed light on biochemical improvements that facilitate versatile applications. ...
Source: Current Opinion in Chemical Biology - June 29, 2020 Category: Biochemistry Authors: Gjaltema RAF, Rots MG Tags: Curr Opin Chem Biol Source Type: research

Targeting histone acetylation/deacetylation in parasites: an update (2017-2020).
Abstract Histone modifying enzymes have vital roles in the growth and survival of both parasites and humans. Targeting the epigenome can be a new strategy for the treatment of parasitic diseases. Compounds modulating histone acetylation/deacetylation have recently been reported hampering Plasmodium, Schistosoma, Leishmania, and Trypanosoma infections. Beside new histone deacetylase inhibitors, PfGCN5 and bromodomain inhibitors have been recently described to inhibit Plasmodium proliferation. Sm histone deacetylase 8 and SmSIRT2, as well as Leishmania and Trypanosoma sirtuins (SIR2rps), seem to be the most reliable...
Source: Current Opinion in Chemical Biology - June 29, 2020 Category: Biochemistry Authors: Fioravanti R, Mautone N, Rovere A, Rotili D, Mai A Tags: Curr Opin Chem Biol Source Type: research

Single-cell  protein analysis by mass spectrometry.
Single-cell protein analysis by mass spectrometry. Curr Opin Chem Biol. 2020 Jun 26;60:1-9 Authors: Slavov N Abstract Human physiology and pathology arise from the coordinated interactions of diverse single cells. However, analyzing single cells has been limited by the low sensitivity and throughput of analytical methods. DNA sequencing has recently made such analysis feasible for nucleic acids but single-cell protein analysis remains limited. Mass spectrometry is the most powerful method for protein analysis, but its application to single cells faces three major challenges: efficiently deli...
Source: Current Opinion in Chemical Biology - June 26, 2020 Category: Biochemistry Authors: Slavov N Tags: Curr Opin Chem Biol Source Type: research

Sensing cellular biochemistry with fluorescent chemical-genetic hybrids.
Abstract Fluorescent biosensors are powerful tools for the detection of biochemical events inside cells with high spatiotemporal resolution. Biosensors based on fluorescent proteins often suffer from issues with photostability and brightness. On the other hand, hybrid, chemical-genetic systems present unique opportunities to combine the strengths of synthetic, organic chemistry with biological macromolecules to generate exquisitely tailored semisynthetic sensors. PMID: 32580134 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - June 21, 2020 Category: Biochemistry Authors: Gautier A, Tebo AG Tags: Curr Opin Chem Biol Source Type: research

Fluorescent probes for investigating peptidoglycan biosynthesis in mycobacteria.
Abstract Tuberculosis killed 1.5 million people in 2018. Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is the most deadly infectious bacteria in the world. A strength of mycobacterial pathogens - their formidable cell wall - could also be one of their greatest molecular vulnerabilities. As in other bacteria, peptidoglycan (PG) maintenance and integrity is essential to mycobacterial survival. But Mtb PG is unique, and a better understanding of its biosynthetic machinery could lead to new drugs or more effective treatment regimens. Such investigations are being accelerated by the applic...
Source: Current Opinion in Chemical Biology - June 9, 2020 Category: Biochemistry Authors: Beatty KE Tags: Curr Opin Chem Biol Source Type: research

Current processes and future challenges of photoautotrophic production of acetyl-CoA-derived solar fuels and chemicals in cyanobacteria.
Abstract The production of fuels and other valuable chemicals via biological routes has gained significant attention during last decades. Cyanobacteria are prokaryotes that convert solar energy to chemical compounds in vivo in direct processes. Intensive studies have been carried out with the aim of engineering cyanobacteria as microfactories for solar fuel and chemical production. Engineered strains of photosynthetic cyanobacteria can produce different compounds on a proof-of-concept level, but few products show titers comparable with those achieved in heterotrophic organisms. Efficient genetic engineering t...
Source: Current Opinion in Chemical Biology - June 2, 2020 Category: Biochemistry Authors: Miao R, Xie H, Liu X, Lindberg P, Lindblad P Tags: Curr Opin Chem Biol Source Type: research

Engineering Clostridium ljungdahlii as the gas-fermenting cell factory for the production of biofuels and biochemicals.
Abstract Clostridium ljungdahlii is a representative autotrophic gas-fermenting acetogen capable of converting CO2 and CO into biomass and multiple metabolites. The carbon fixation and conversion based on C. ljungdahlii have great potential for the sustainable production of bulk biochemicals and biofuels using industrial syngas and waste gases. With substantial recent advances in genetic manipulation tools, it has become possible to study and improve the metabolic capability of C. ljungdahlii in gas fermentation. The product scope of C. ljungdahlii has been expanded through the introduction of heter...
Source: Current Opinion in Chemical Biology - May 29, 2020 Category: Biochemistry Authors: Zhang L, Zhao R, Jia D, Jiang W, Gu Y Tags: Curr Opin Chem Biol Source Type: research

Recent advances in glycan synthesis.
Abstract Carbohydrates play important roles in life science, but their synthesis is always hampered by their complicated chemical structures. Scientists have never stopped trying to solve the problem of glycan synthesis from various aspects. Here a brief overview of recent progress in glycan synthesis, including chemical approaches, chemoenzymatic approaches, and automated synthesis, will be discussed, focusing on the efficiency of new glycosylation methods, the stereoselectivity of coupled products, and their applications in the assembly of complex glycan chains. PMID: 32480314 [PubMed - as supplied by publi...
Source: Current Opinion in Chemical Biology - May 29, 2020 Category: Biochemistry Authors: Li BH, Ye XS Tags: Curr Opin Chem Biol Source Type: research

Towards a more precise therapy in cancer: Exploring epigenetic complexity.
sco M Abstract A plethora of preclinical evidences suggests that pharmacological targeting of epigenetic dysregulation is a potent strategy to combat human diseases. Nevertheless, the implementation of epidrugs in clinical practice is very scarce and mainly limited to haematological malignancies. In this review, we discuss cutting-edge strategies to foster the chemical design, the biological rationale and the clinical trial development of epidrugs. Specifically, we focus on the development of dual hybrids to exploit multitargeting of key epigenetic molecules deregulated in cancer; the study of epigenetic-synthetic...
Source: Current Opinion in Chemical Biology - May 29, 2020 Category: Biochemistry Authors: Cossío FP, Esteller M, Berdasco M Tags: Curr Opin Chem Biol Source Type: research

Toolbox for chemically synthesized histone proteins.
Abstract Histone post-translational modifications play significant roles in gene regulation processes. Among many approaches, chemical protein synthesis has been a successful and promising method for the preparation of homogeneous products of site-specifically modified histones for elucidation of their biological significance. In this short review, we describe the recent advances in synthetic toolbox for histone proteins such as thioester precursors, chemical ubiquitination, and one-pot peptide ligation. PMID: 32473259 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - May 27, 2020 Category: Biochemistry Authors: Nakatsu K, Hayashi G, Okamoto A Tags: Curr Opin Chem Biol Source Type: research

Fluorogenic probes for imaging cellular phosphatase activity.
Abstract The ability to visualize enzyme activity in a cell, tissue, or living organism can greatly enhance our understanding of the biological roles of that enzyme. While many aspects of cellular signaling are controlled by reversible protein phosphorylation, our understanding of the biological roles of the protein phosphatases involved is limited. Here, we provide an overview of progress toward the development of fluorescent probes that can be used to visualize the activity of protein phosphatases. Significant advances include the development of probes with visible and near-infrared (near-IR) excitation and...
Source: Current Opinion in Chemical Biology - May 26, 2020 Category: Biochemistry Authors: McCullough BS, Barrios AM Tags: Curr Opin Chem Biol Source Type: research