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Current Opinion in Chemical Biology

Edward J Crane
A wide group of microbes are able to "make a living" on Earth by basing their energetic metabolism on inorganic sulfur compounds. Because of their range of stable redox states, sulfur and inorganic sulfur compounds can be utilized as either oxidants or reductants in a diverse array of energy-conserving reactions. In this review the major enzymes and basic chemistry of sulfur-based respiration and chemolithotrophy are outlined. The reversibility and versatility of these enzymes, however, means that they can often be used in multiple ways, and several cases are discussed in which enzymes which are considered to be hallmarks of a particular respiratory or lithotrophic process have been found to be used in other, often opposing, metabolic processes...
February 7, 2019: Current Opinion in Chemical Biology
Kerry M Dorr, Frank L Conlon
Congenital malformations, or structural birth defects, are now the leading cause of infant mortality in the United States and Europe (Dolk et al., 2010; Heron et al., 2009). Of the congenital malformations, congenital heart disease (CHD) is the most common (Dolk et al., 2010; Heron et al., 2009). Thus, a molecular understanding of heart development is an essential goal for improving clinical approaches to CHD. However, CHDs are commonly a result of genetic defects that manifest themselves in a spatial and temporal manner during the early stages of embryogenesis, leaving them mostly intractable to mass spectrometry-based analysis...
January 31, 2019: Current Opinion in Chemical Biology
Emma K Davison, Margaret A Brimble
The biological activity and structural diversity of natural products are unsurpassed by any available synthetic screening libraries. As such, these privileged scaffolds serve as important, biologically prevalidated platforms for the design of compound libraries in the search for new drug candidates. Recent progress has focussed on improving the potency, selectivity and pharmacokinetics of bioactive natural products through structural modification, leading to the emergence of a number of drug-like lead compounds...
January 22, 2019: Current Opinion in Chemical Biology
Jonathan D Caranto
Nitric oxide (NO) has a broad range of biological utilities including as a biosynthon for bacterial natural products (NPs). The biosyntheses of thaxtomin A and rufomycin require an NO-dependent nitration step where a bacterial NO synthase provides the necessary NO and nitration is catalyzed by a cytochrome P450 homolog. Undiscovered NO-dependent biosynthesis pathways are likely to have similar requirements: a pathway dedicated NO source and a metalloenzyme to catalyze the NO-dependent chemistry. This review discusses the current literature on NO-dependent nitration biosynthesis and relevant enzyme mechanisms...
January 10, 2019: Current Opinion in Chemical Biology
Jinhyun Kim, Chan Beum Park
Redox biocatalysis has come to the forefront because of its excellent catalytic efficiency, stereoselectivity, and environmental benignity. The green and sustainable biotransformation can be driven by photoelectrochemical (PEC) platforms where redox biocatalysis is coupled with photoelectrocatalysis. The main challenge is how to transfer photoexcited electrons to (or from) the enzyme redox centers for effective biotransformation using solar energy. This review commences with a conceptual discussion of biocatalytic PEC platforms and highlights recent advances in PEC-based biotransformation through cofactor regeneration or direct transfer of charge carriers to (or from) oxidoreductases on enzyme-conjugated electrodes...
January 3, 2019: Current Opinion in Chemical Biology
Kouta Takeda, Kiwamu Umezawa, Anikó Várnai, Vincent Gh Eijsink, Kiyohiko Igarashi, Makoto Yoshida, Nobuhumi Nakamura
In 2014, the first fungal pyrroloquinoline-quinone (PQQ)-dependent enzyme was discovered as a pyranose dehydrogenase from the basidiomycete Coprinopsis cinerea (CcPDH). This discovery laid the foundation for a new Auxiliary Activities (AA) family, AA12, in the Carbohydrate-Active enZymes (CAZy) database and revealed a novel enzymatic activity potentially involved in biomass conversion. This review summarizes recent progress made in research on this fungal oxidoreductase and related enzymes. CcPDH consists of the catalytic PQQ-binding AA12 domain, an N-terminal cytochrome b AA8 domain, and a C-terminal family 1 carbohydrate-binding module (CBM1)...
December 20, 2018: Current Opinion in Chemical Biology
Laurent Gatto, Lisa M Breckels, Kathryn S Lilley
The sub-cellular localisation of a protein is vital in defining its function, and a protein's mis-localisation is known to lead to adverse effect. As a result, numerous experimental techniques and datasets have been published, with the aim of deciphering the localisation of proteins at various scales and resolutions, including high profile mass spectrometry-based efforts. Here, we present a meta-analysis assessing and comparing the sub-cellular resolution of 29 such mass spectrometry-based spatial proteomics experiments using a newly developed tool termed QSep...
December 13, 2018: Current Opinion in Chemical Biology
Christopher K Prier, Birgit Kosjek
Redox enzymes offer many powerful transformations for the efficient industrial-scale synthesis of diverse chemicals desired by society. Here we survey recent preparative applications of redox enzymes, highlighting both mature enzyme platforms and promising technologies for future applications. While in some cases commercial enzymes can be employed directly on industrial scales, in other cases protein engineering is necessary to evolve an enzyme fit for non-biological substrates and conditions. Both approaches require the input of process engineering to properly balance the needs of the enzymatic chemistry with the requirements for an industrial process...
December 12, 2018: Current Opinion in Chemical Biology
Claudia Schmid-Dannert, Fernando López-Gallego
During the past decades, biocatalysis has made important contributions to chemical manufacturing by using both whole-cell and cell-free biotransformation reactions. More recently, multi-enzyme systems that can run step-wise reactions in one-pot with high selectivity are increasingly being developed. The use of multiple isolated enzymes to perform a series of reactions offers operational and process advantages over the use of living or resting cells, but such cell free processes need to be optimized to meet industrial productivity and titer requirements...
December 11, 2018: Current Opinion in Chemical Biology
Dalila Bensaddek, Armel Nicolas, Angus I Lamond
Proteomes are highly dynamic and can respond rapidly to environmental and cellular signals. Within cells, proteins often form distinct pools with different functions and properties. However, in quantitative proteomics studies it is common to measure averaged values for proteins that do not reflect variations that may occur between different protein isoforms, different subcellular compartments, or in cells at different cell cycle stages and so on. Here we review experimental approaches that can be used to enhance the signal from specific pools of protein that may otherwise be obscured through averaging across protein populations...
December 11, 2018: Current Opinion in Chemical Biology
Lars Lauterbach, Oliver Lenz
Solar-driven electrolysis enables sustainable production of molecular hydrogen (H2 ), which represents a cheap and carbon-free reductant. Knallgas bacteria like Ralstonia eutropha are able to split H2 to supply energy in form of ATP and NADH, which can be subsequently used to power reactions of interest. R. eutropha employs the Calvin-Benson-Bassham cycle for the fixation of CO2 , which is considered as an abundant and non-competing raw material. In this article, we summarize state-of-the-art approaches for H2 -driven biosyntheses using engineered R...
December 10, 2018: Current Opinion in Chemical Biology
David G Rattray, Leonard J Foster
Identifying protein-protein interactions (PPIs) is necessary to understand the molecular mechanisms behind cellular processes. This task is complicated by the facts that many proteins can interact simultaneously (i.e. a protein complex) and may participate in more than one distinct complex. Because of this, a large number of combinatorial arrangements are possible, both of PPIs and complexes, making it a difficult task to identify all truly interacting proteins. Protein interactions also range from stable to highly transient assemblies, with lifetimes on the order of seconds [1]...
December 4, 2018: Current Opinion in Chemical Biology
Alexander G Goglia, Jared E Toettcher
Cells sense, process, and respond to extracellular information using signaling networks: collections of proteins that act as precise biochemical sensors. These protein networks are characterized by both complex temporal organization, such as pulses of signaling activity, and by complex spatial organization, where proteins assemble structures at particular locations and times within the cell. Yet despite their ubiquity, studying these spatial and temporal properties has remained challenging because they emerge from the entire protein network rather than a single node, and cannot be easily tuned by drugs or mutations...
December 4, 2018: Current Opinion in Chemical Biology
Daniel W Bak, Tyler J Bechtel, Julia A Falco, Eranthie Weerapana
Cysteine residues are concentrated at key functional sites within proteins, performing diverse roles in metal binding, catalysis, and redox chemistry. Chemoproteomic platforms to interrogate the reactive cysteinome have developed significantly over the past 10 years, resulting in a greater understanding of cysteine functionality, modification, and druggability. Recently, chemoproteomic methods to examine reactive cysteine residues from specific subcellular organelles have provided significantly improved proteome coverage and highlights the unique functionalities of cysteine residues mediated by cellular localization...
November 30, 2018: Current Opinion in Chemical Biology
Daniel Jh Nightingale, Aikaterini Geladaki, Lisa M Breckels, Stephen G Oliver, Kathryn S Lilley
Subcellular protein localisation is essential for the mechanisms that govern cellular homeostasis. The ability to understand processes leading to this phenomenon will therefore enhance our understanding of cellular function. Here we review recent developments in this field with regard to mass spectrometry, fluorescence microscopy and computational prediction methods. We highlight relative strengths and limitations of current methodologies focussing particularly on studies in the yeast Saccharomyces cerevisiae...
November 29, 2018: Current Opinion in Chemical Biology
John A Gerlt, Tobias J Erb
No abstract text is available yet for this article.
November 26, 2018: Current Opinion in Chemical Biology
Ileana M Cristea, Kathryn S Lilley
No abstract text is available yet for this article.
February 2019: Current Opinion in Chemical Biology
Sumedh Joshi, Dmytro Fedoseyenko, Nilkamal Mahanta, Hannah Manion, Saad Naseem, Tohru Dairi, Tadhg P Begley
The recently discovered futalosine-dependent menaquinone biosynthesis pathway employs radical chemistry for the naphthoquinol core assembly. Mechanistic studies on this pathway have resulted in the discovery of novel reaction motifs. MqnA is the first example of a chorismate dehydratase. MqnE is the first example of a radical SAM enzyme that catalyzes the addition of the 5'-deoxyadenosyl radical to the substrate double bond rather than hydrogen atom abstraction. Both MqnE and MqnC reaction sequences involve radical additions to a benzene ring followed by formation of an aryl radical anion intermediate...
December 2018: Current Opinion in Chemical Biology
Paul Dean, Tiaan Heunis, Anetta Härtlova, Matthias Trost
Phagosomes are highly dynamic organelles formed by the uptake of particles through phagocytic innate immune cells such as macrophages. Their key roles in microbe elimination and antigen presentation make them essential for innate and adaptive immunity. However, phagosomes are also important for tissue homeostasis as even in healthy individuals billions of dead cells are phagocytosed each day. In this short review, we highlight how the use of latex beads as inert baits for phagocytosis and subsequent analysis by proteomics has changed our understanding of the phagosome...
November 24, 2018: Current Opinion in Chemical Biology
Daniel J Ryan, Jeffrey M Spraggins, Richard M Caprioli
Matrix assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is a powerful technology used to investigate the spatial distributions of thousands of molecules throughout a tissue section from a single experiment. As proteins represent an important group of functional molecules in tissue and cells, the imaging of proteins has been an important point of focus in the development of IMS technologies and methods. Protein identification is crucial for the biological contextualization of molecular imaging data...
November 23, 2018: Current Opinion in Chemical Biology
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