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A Potent HDAC Inhibitor, 1-Alaninechlamydocin, from a Tolypocladium sp. Induces G2/M Cell Cycle Arrest and Apoptosis in MIA PaCa-2 Cells

A Potent HDAC Inhibitor, 1-Alaninechlamydocin, from a Tolypocladium sp. Induces G2/M Cell Cycle Arrest and Apoptosis in MIA PaCa-2 Cells | Natural Products Chemistry Breaking News | Scoop.it

The cyclic tetrapeptide 1-alaninechlamydocin was purified from a Great Lakes-derived fungal isolate identified as a Tolypocladium sp. Although the planar structure was previously described, a detailed analysis of its spectroscopic data and biological activity are reported here for the first time. Its absolute configuration was determined using a combination of spectroscopic (1H–1H ROESY, ECD, and X-ray diffraction) and chemical (Marfey’s analysis) methods. 1-Alaninechlamydocin showed potent antiproliferative/cytotoxic activities in a human pancreatic cancer cell line (MIA PaCa-2) at low-nanomolar concentrations (GI50 5.3 nM, TGI 8.8 nM, LC50 22 nM). Further analysis revealed that 1-alaninechlamydocin induced G2/M cell cycle arrest and apoptosis. Similar to other cyclic epoxytetrapeptides, the inhibitory effects of 1-alaninechlamydocin are proposed to be produced primarily via inhibition of histone deacetylase (HDAC) activity.


J. Nat. Prod., Article ASAP
DOI: 10.1021/np500387h


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A Plausible Simultaneous Synthesis of Amino Acids and Simple Peptides on the Primordial Earth

A Plausible Simultaneous Synthesis of Amino Acids and Simple Peptides on the Primordial Earth | Natural Products Chemistry Breaking News | Scoop.it

Following his seminal work in 1953, Stanley Miller conducted an experiment in 1958 to study the polymerization of amino acids under simulated early Earth conditions. In the experiment, Miller sparked a gas mixture of CH4, NH3, and H2O, while intermittently adding the plausible prebiotic condensing reagent cyanamide. For unknown reasons, an analysis of the samples was not reported. We analyzed the archived samples for amino acids, dipeptides, and diketopiperazines by liquid chromatography, ion mobility spectrometry, and mass spectrometry. A dozen amino acids, 10 glycine-containing dipeptides, and 3 glycine-containing diketopiperazines were detected. Miller’s experiment was repeated and similar polymerization products were observed. Aqueous heating experiments indicate that Strecker synthesis intermediates play a key role in facilitating polymerization. These results highlight the potential importance of condensing reagents in generating diversity within the prebiotic chemical inventory.


  1. Eric T. Parker1,
  2. Dr. Manshui Zhou1,
  3. Dr. Aaron S. Burton2,
  4. Dr. Daniel P. Glavin3,
  5. Dr. Jason P. Dworkin3,
  6. Prof. Dr. Ramanarayanan Krishnamurthy4,
  7. Prof. Dr. Facundo M. Fernández1,* and
  8. Prof. Dr. Jeffrey L. Bada


Angewandte Chemie International Edition

DOI: 10.1002/anie.201403683

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Fungi borrowed bacterial gene again and again

Fungi borrowed bacterial gene again and again | Natural Products Chemistry Breaking News | Scoop.it
Multiple independent gene transfers gave fungi ability to colonize plant roots.



A single gene from bacteria has been donated to fungi on at least 15 occasions. The discovery shows that an evolutionary shortcut once thought to be restricted to bacteria is surprisingly common in more complex, eukaryotic life.

Bacteria frequently trade genes back and forth with their neighbours, gaining abilities and traits that enable them to adapt quickly to new environments. More complex organisms, by contrast, generally have to make do with the slow process of gene duplication and mutation.

There are a few examples of gene swapping between eukaryotes — the domain of life that includes fungi, plants and animals — and even from bacteria to eukaryotes (see 'Bacterial gene helps coffee beetle get its fix'). But such events, known as horizontal gene transfer, were thought to be rare. 

But Daniel Muller, a microbial ecologist at the University of Lyons in France, and his colleagues have cast doubt on that assumption after studying bacteria in the soil around the roots of plants. They found that the bacterial gene acdS, used to promote the growth of plant roots, was also present in several types of fungus. Their work is published today in Proceedings of the Royal Society B


Bruto, M., Prigent-Combaret, C., Luis, P., Moënne-Loccoz, Y. & Muller, D. Proc. R. Soc. B. http://dx.doi.org/10.1098/rspb.2014.0848 (2014).

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Natural products containing ‘decalin’ motif in microorganisms

Natural products containing ‘decalin’ motif in microorganisms | Natural Products Chemistry Breaking News | Scoop.it

Microorganisms are well-known producers of a wide variety of bioactive compounds that are utilized not only for their primary metabolism but also for other purposes such as defense, detoxification, or communication with other micro- and macro-organisms. Natural products containing a ‘decalin ring’ occur often in microorganisms. They exhibit diverse and remarkable biological activities, including antifungal, antibacterial, anticancer and immunosuppressive activities, to name a few. This review surveys the natural decalin-type compounds that have been isolated from microorganisms, with emphasis on both chemical and biological implications. Total syntheses of some important decalin moiety-containing natural products are also highlighted.


Gang Li,a   Souvik Kusari*a and   Michael Spiteller*a  
Show Affiliations
Nat. Prod. Rep., 2014, Advance Article


DOI: 10.1039/C4NP00031E


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Aspergillomarasmine A overcomes metallo-[bgr]-lactamase antibiotic resistance

Aspergillomarasmine A overcomes metallo-[bgr]-lactamase antibiotic resistance | Natural Products Chemistry Breaking News | Scoop.it

The emergence and spread of carbapenem-resistant Gram-negative pathogens is a global public health problem. The acquisition of metallo-β-lactamases (MBLs) such as NDM-1 is a principle contributor to the emergence of carbapenem-resistant Gram-negative pathogens that threatens the use of penicillin, cephalosporin and carbapenem antibiotics to treat infections. To date, a clinical inhibitor of MBLs that could reverse resistance and re-sensitize resistant Gram-negative pathogens to carbapenems has not been found. Here we have identified a fungal natural product, aspergillomarasmine A (AMA), that is a rapid and potent inhibitor of the NDM-1 enzyme and another clinically relevant MBL, VIM-2. AMA also fully restored the activity of meropenem against Enterobacteriaceae, Acinetobacter spp. and Pseudomonas spp. possessing either VIM or NDM-type alleles. In mice infected with NDM-1-expressing Klebsiella pneumoniae, AMA efficiently restored meropenem activity, demonstrating that a combination of AMA and a carbapenem antibiotic has therapeutic potential to address the clinical challenge of MBL-positive carbapenem-resistant Gram-negative pathogens.


Nature
 
510,
 
503–506
 
(26 June 2014)
 
doi:10.1038/nature13445


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Structural diversity and bioactivities of natural benzophenones

Structural diversity and bioactivities of natural benzophenones | Natural Products Chemistry Breaking News | Scoop.it

Natural benzophenones are a class of compounds consisting of more than 300 members, which exhibit great structural diversity and bioactive properties. Many benzophenones have been reported from higher plants or fungi, most with polyisoprenylated benzophenone skeletons, and are mainly found in the Clusiaceae (formerly Guttiferae) family, a number from edible or medicinal species. Owing to their variable substituents and complex ring systems, many new polyisoprenylated benzophenones (PPBS), including ones with unusual skeletons, were isolated and identified. These natural benzophenones exhibit a range of biological activities including antifungal, anti-HIV, antimicrobial, antioxidant, antiviral and cytotoxic. Because of the increased numbers and biological importance of these unique natural product polyphenols, we will review natural benzophenones and provide an in-depth discussion of their structural diversity and biological activity. By focusing on these key developments in benzophenones, we will contribute a focused review, selecting examples mostly from the last 15 years, but extending our scope to other historically important benzophenones discovered prior to that time.


Shi-Biao Wu,ab   Chunlin Long*a and   Edward J. Kennelly*ab  
Show Affiliations
Nat. Prod. Rep., 2014, Advance Article


DOI: 10.1039/C4NP00027G

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Interactive XCMS Online: Simplifying Advanced Metabolomic Data Processing and Subsequent Statistical Analyses

Interactive XCMS Online: Simplifying Advanced Metabolomic Data Processing and Subsequent Statistical Analyses | Natural Products Chemistry Breaking News | Scoop.it

XCMS Online (xcmsonline.scripps.edu) is a cloud-based informatic platform designed to process and visualize mass-spectrometry-based, untargeted metabolomic data. Initially, the platform was developed for two-group comparisons to match the independent, “control” versus “disease” experimental design. Here, we introduce an enhanced XCMS Online interface that enables users to perform dependent (paired) two-group comparisons, meta-analysis, and multigroup comparisons, with comprehensive statistical output and interactive visualization tools. Newly incorporated statistical tests cover a wide array of univariate analyses. Multigroup comparison allows for the identification of differentially expressed metabolite features across multiple classes of data while higher order meta-analysis facilitates the identification of shared metabolic patterns across multiple two-group comparisons. Given the complexity of these data sets, we have developed an interactive platform where users can monitor the statistical output of univariate (cloud plots) and multivariate (PCA plots) data analysis in real time by adjusting the threshold and range of various parameters. On the interactive cloud plot, metabolite features can be filtered out by their significance level (p-value), fold change, mass-to-charge ratio, retention time, and intensity. The variation pattern of each feature can be visualized on both extracted-ion chromatograms and box plots. The interactive principal component analysis includes scores, loadings, and scree plots that can be adjusted depending on scaling criteria. The utility of XCMS functionalities is demonstrated through the metabolomic analysis of bacterial stress response and the comparison of lymphoblastic leukemia cell lines.


Anal. Chem., Article ASAP
DOI: 10.1021/ac500734c




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The Chemical Arsenal of Burkholderia pseudomallei Is Essential for Pathogenicity

The Chemical Arsenal of Burkholderia pseudomallei Is Essential for Pathogenicity | Natural Products Chemistry Breaking News | Scoop.it

Increasing evidence has shown that small-molecule chemistry in microbes (i.e., secondary metabolism) can modulate the microbe–host response in infection and pathogenicity. The bacterial disease melioidosis is conferred by the highly virulent, antibiotic-resistant pathogenBurkholderia pseudomallei (BP). Whereas some macromolecular structures have been shown to influence BP virulence (e.g., secretion systems, cellular capsule, pili), the role of the large cryptic secondary metabolome encoded within its genome has been largely unexplored for its importance to virulence. Herein we demonstrate that BP-encoded small-molecule biosynthesis is indispensible for in vivo BP pathogenicity. Promoter exchange experiments were used to induce high-level molecule production from two gene clusters (MPN and SYR) found to be essential for in vivo virulence. NMR structural characterization of these metabolites identified a new class of lipopeptide biosurfactants/biofilm modulators (the malleipeptins) and syrbactin-type proteasome inhibitors, both of which represent overlooked small-molecule virulence factors for BP. Disruption of Burkholderia virulence by inhibiting the biosynthesis of these small-molecule biosynthetic pathways may prove to be an effective strategy for developing novel melioidosis-specific therapeutics.


J. Am. Chem. Soc., Article ASAP
DOI: 10.1021/ja504617n


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γ-Hydroxynitrile glucosides from the seeds of Prinsepia utilis

γ-Hydroxynitrile glucosides from the seeds of Prinsepia utilis | Natural Products Chemistry Breaking News | Scoop.it

γ-Hydroxynitrile glucosides (prinsepicyanosides A–E) were isolated alongside 11 known compounds from seeds of Prinsepia utilis Royle. Their structures were determined by detailed analysis of NMR and MS spectroscopic data. The relative configuration of prinsepicyanoside C was established by Cu-Kα X-ray crystallography. Prinsepicyanoside A, osmaronin, and 4-(hydroxylmethyl)-5H-furan-2-one exhibited borderline antibacterial activity against Salmonella gallinarum, Vibrio parahaemolyticus, and Vibrio cholera with MIC values of 30.1, 20.7, and 22.8 μg/mL, respectively.



Available online 18 June 2014

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Multiplex genome editing by natural transformation

Significance

The ability to generate mutants is essential in microbiology research. Although methods have been developed for making defined single mutations in bacterial genomes, methods for simultaneously generating multiple defined mutations (i.e., multiplex genome editing) have been limited to model species such as Escherichia coli. Diverse microbial species have the ability to take up exogenous DNA naturally and integrate it into their genome, a process known as “natural transformation.” Although natural transformation has been exploited for making single mutations, it has not been used previously for multiplex genome editing. Here, we describe multiplex genome editing by natural transformation and demonstrate the utility of this method in two naturally competent microbial species. This method should be broadly applicable for diverse research applications.


  1. Ankur B. Daliaa,
  2. EmilyKate McDonougha, and
  3. Andrew Camillia,b,1

PNAS

Ankur B. Dalia,  8937–8942, doi: 10.1073/pnas.1406478111

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Elucidation of Pseurotin Biosynthetic Pathway Points to Trans-Acting C-Methyltransferase: Generation of Chemical Diversity

Elucidation of Pseurotin Biosynthetic Pathway Points to Trans-Acting C-Methyltransferase: Generation of Chemical Diversity | Natural Products Chemistry Breaking News | Scoop.it

Pseurotins comprise a family of structurally related Aspergillal natural products having interesting bioactivity. However, little is known about the biosynthetic steps involved in the formation of their complex chemical features. Systematic deletion of the pseurotin biosynthetic genes in A. fumigatus and in vivo and in vitro characterization of the tailoring enzymes to determine the biosynthetic intermediates, and the gene products responsible for the formation of each intermediate, are described. Thus, the main biosynthetic steps leading to the formation of pseurotin A from the predominant precursor, azaspirene, were elucidated. The study revealed the combinatorial nature of the biosynthesis of the pseurotin family of compounds and the intermediates. Most interestingly, we report the first identification of an epoxidase C-methyltransferase bifunctional fusion protein PsoF which appears to methylate the nascent polyketide backbone carbon atom in trans.



Dr. Yuta Tsunematsu1,Manami Fukutomi1,Dr. Takayoshi Saruwatari1,Prof. Dr. Hiroshi Noguchi1,Prof. Dr. Kinya Hotta2,Prof. Dr. Yi Tang3 and Prof. Dr. Kenji Watanabe

Angewandte Chemie International Edition


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Nature’s Palette: The Search for Natural Blue Colorants

Nature’s Palette: The Search for Natural Blue Colorants | Natural Products Chemistry Breaking News | Scoop.it
NatProdChem's insight:

The food and beverage industry is seeking to broaden the palette of naturally derived colorants. Although considerable effort has been devoted to the search for new blue colorants in fruits and vegetables, less attention has been directed towards blue compounds from other sources such as bacteria and fungi. The current work reviews known organic blue compounds from natural plant, animal, fungal, and microbial sources. The scarcity of blue colored metabolites in the natural world relative to metabolites of other colors is discussed and structural trends common among natural blue compounds are identified. These compounds are grouped into seven structural classes and evaluated for their potential as new color additives.



J. Agric. Food Chem., Just Accepted Manuscript
DOI: 10.1021/jf501419q
Publication Date (Web): June 13, 2014
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Synthetic receptor recognises entire drug family | Chemistry World

Synthetic receptor recognises entire drug family | Chemistry World | Natural Products Chemistry Breaking News | Scoop.it
Supramolecular structure could be used to monitor the rise of new 'designer' drugs excreted into sewers
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Aston's mass spectrograph | Chemistry World

Aston's mass spectrograph | Chemistry World | Natural Products Chemistry Breaking News | Scoop.it
Discoveries en masse


How long does it take to make a major discovery? Sometimes it takes decades of painstaking work, methodically sifting and analysing reams of data. And yet at other times, a flurry of intense toil leads rapidly to a revelation. At the dawn of the 20th century, a cascade of world-changing discoveries were made, rewriting the textbooks almost every year. A century later, it is easy to disregard how difficult and mysterious the work was, and none more so than the composition of the atom.

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Miller’s forgotten experiments point to primitive protein genesis | Chemistry World

Miller’s forgotten experiments point to primitive protein genesis | Chemistry World | Natural Products Chemistry Breaking News | Scoop.it
50-year-old test tubes hold clues to formation of peptide bonds – and life – on early Earth
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Metachelins, Mannosylated and N-Oxidized Coprogen-Type Siderophores from Metarhizium robertsii

Metachelins, Mannosylated and N-Oxidized Coprogen-Type Siderophores from Metarhizium robertsii | Natural Products Chemistry Breaking News | Scoop.it

Under iron-depleted culture conditions, the entomopathogenic fungus Metarhizium robertsii (Bischoff, Humber, and Rehner) (= M. anisopliae) produces a complex of extracellular siderophores including novel O-glycosylated and N-oxidized coprogen-type compounds as well as the known fungal siderophores Nα-dimethylcoprogen (NADC) and dimerumic acid (DA). Metachelin A (1), the most abundant component in the M. robertsii siderophore mixture, was characterized as a 1094 Da analogue of NADC that is O-glycosylated by β-mannose at both terminal hydroxyl groups and N-oxidized at the dimethylated α-nitrogen. The mixture also contained a 1078 Da analogue, metachelin B (2), which lacks the N-oxide modification. Also characterized were the aglycone of 1, i.e., the N-oxide of NADC (3), and the monomannoside of DA (6). N-Oxide and O-glycosyl substituents are unprecedented among microbial siderophores. At high ESIMS source energy and at room temperature in DMSO, 1 underwent Cope elimination, resulting in loss of the Nα-dimethyl group and dehydration of the α–β bond. High-resolution ESIMS data confirmed that all tri- and dihydroxamate siderophores (16) complex with trivalent Fe, Al, and Ga. In a chrome azurol S assay, all of the M. robertsii siderophores showed iron-binding activity roughly equivalent to that of desferrioxamine B.


J. Nat. Prod., Article ASAP
DOI: 10.1021/np500300s
Publication Date (Web): July 3, 2014
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Metabolite profiling in LC–DAD using multivariate curve resolution: the alsace package for R

Abstract

For those chemical compounds absorbing in the UV–Vis region and not readily applicable to routine mass spectrometry ionisation methods, liquid chromatography coupled to diode array detection is a convenient platform to perform metabolite profiling. Data processing by hand is labour-intensive and error prone. In the present study a strategy based on multivariate curve resolution, and its implementation in an R package called alsace are described. The final result of an analysis is a table containing peak heights or peak areas for all features of the individual injections. The capabilities of the software, providing elements such as splitting the data into separate, possibly overlapping time windows, merging the results of the individual time windows, and parametric time warping to align features, are illustrated using a cassava-derived data set.

July 2014

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Acanthomanzamines A–E with New Manzamine Frameworks from the Marine Sponge Acanthostrongylophora ingens

Acanthomanzamines A–E with New Manzamine Frameworks from the Marine Sponge Acanthostrongylophora ingens | Natural Products Chemistry Breaking News | Scoop.it

Five new manzamine alkaloids, acanthomanzamines A–E, were isolated from the marine sponge Acanthostrongylophora ingens. Acanthomanzamines A and B are the first examples, containing a tetrahydroisoquinoline instead of a β-carboline in manzamine-related alkaloids. Acanthomanzamine C contains a hexahydrocyclopenta[b]pyrrol-4(2H)-one ring that may be converted from an eight-membered ring in manzamine A. Acanthomanzamines D and E have an additional oxazolidine and 2-methyloxazolidine rings, respectively, which fuse to the manzamine skeleton.


Org. Lett., Article ASAP
DOI: 10.1021/ol5015569



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RAMClust: A Novel Feature Clustering Method Enables Spectral-Matching-Based Annotation for Metabolomics Data

RAMClust: A Novel Feature Clustering Method Enables Spectral-Matching-Based Annotation for Metabolomics Data | Natural Products Chemistry Breaking News | Scoop.it

Metabolomic data are frequently acquired using chromatographically coupled mass spectrometry (MS) platforms. For such datasets, the first step in data analysis relies on feature detection, where a feature is defined by a mass and retention time. While a feature typically is derived from a single compound, a spectrum of mass signals is more a more-accurate representation of the mass spectrometric signal for a given metabolite. Here, we report a novel feature grouping method that operates in an unsupervised manner to group signals from MS data into spectra without relying on predictability of the in-source phenomenon. We additionally address a fundamental bottleneck in metabolomics, annotation of MS level signals, by incorporating indiscriminant MS/MS (idMS/MS) data implicitly: feature detection is performed on both MS and idMS/MS data, and feature–feature relationships are determined simultaneously from the MS and idMS/MS data. This approach facilitates identification of metabolites using in-source MS and/or idMS/MS spectra from a single experiment, reduces quantitative analytical variation compared to single-feature measures, and decreases false positive annotations of unpredictable phenomenon as novel compounds. This tool is released as a freely available R package, called RAMClustR, and is sufficiently versatile to group features from any chromatographic-spectrometric platform or feature-finding software.


Anal. Chem., Article ASAP
DOI: 10.1021/ac501530d
Publication Date (Web): June 13, 2014


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Hot off the press - Natural Product Reports (RSC Publishing)

Hot off the press - Natural Product Reports (RSC Publishing) | Natural Products Chemistry Breaking News | Scoop.it
A personal selection of 32 recent papers is presented covering various aspects of current developments in bioorganic chemistry and novel natural products such as logeracemin A from Daphniphyllum longeracemosum.
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Bioinspired Total Synthesis of Sespenine

Bioinspired Total Synthesis of Sespenine | Natural Products Chemistry Breaking News | Scoop.it
Abstract

The first total synthesis of sespenine, a rare indole sesquiterpenoid from a mangrove endophyte, has been accomplished. A bioinspired aza-Prins/Friedel–Crafts/retro Friedel–Crafts cascade reaction assembles the bridged tetrahydroquinoline core. Further investigations on the aza-Prins cyclization imply that the C3 configuration of the hydroxyindolenine intermediate is crucial to the biosynthesis of sespenine and its congener xiamycin A.


  1. Yu Sun1,‡, 
  2. Pengxi Chen1,‡, 
  3. Deliang Zhang1, 
  4. Martin Baunach2, 
  5. Prof. Dr. Christian Hertweck2 and
  6. Prof. Dr. Ang Li
Angewandte Chemie International Edition

Article first published online: 24 JUN 2014

DOI: 10.1002/anie.201404191

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Biosynthesis: A carbonate architect emerges

Biosynthesis: A carbonate architect emerges | Natural Products Chemistry Breaking News | Scoop.it
Carbonates are known to exist in natural products, but their biosynthesis has not been linked to any enzymes. An unusual fungal Baeyer-Villiger monooxygenase CcsB is now revealed to catalyze an in-line carbonate formation via a two-step mechanism of oxygen atom insertions.
NatProdChem's insight:

Nature Chemical Biology 10, 486 487 (2014) doi:10.1038/nchembio.1531

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Structure of a modular polyketide synthase

Structure of a modular polyketide synthase | Natural Products Chemistry Breaking News | Scoop.it

Polyketide natural products constitute a broad class of compounds with diverse structural features and biological activities. Their biosynthetic machinery, represented by type I polyketide synthases (PKSs), has an architecture in which successive modules catalyse two-carbon linear extensions and keto-group processing reactions on intermediates covalently tethered to carrier domains. Here we used electron cryo-microscopy to determine sub-nanometre-resolution three-dimensional reconstructions of a full-length PKS module from the bacterium Streptomyces venezuelae that revealed an unexpectedly different architecture compared to the homologous dimeric mammalian fatty acid synthase. A single reaction chamber provides access to all catalytic sites for the intramodule carrier domain. In contrast, the carrier from the preceding module uses a separate entrance outside the reaction chamber to deliver the upstream polyketide intermediate for subsequent extension and modification. This study reveals for the first time, to our knowledge, the structural basis for both intramodule and intermodule substrate transfer in polyketide synthases, and establishes a new model for molecular dissection of these multifunctional enzyme systems.


Nature
(2014)
doi:10.1038/nature13423
Received
07 May 2013
Accepted
01 May 2014
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Plant Responses to Bacterial N-Acyl l-Homoserine Lactones are Dependent on Enzymatic Degradation to l-Homoserine

Plant Responses to Bacterial N-Acyl l-Homoserine Lactones are Dependent on Enzymatic Degradation to l-Homoserine | Natural Products Chemistry Breaking News | Scoop.it

Many bacteria use quorum sensing (QS) to regulate phenotypes that ultimately benefit the bacterial population at high cell densities. These QS-dependent phenotypes are diverse and can have significant impacts on the bacterial host, including virulence factor production, motility, biofilm formation, bioluminescence, and root nodulation. As bacteria and their eukaryotic hosts have coevolved over millions of years, it is not surprising that certain hosts appear to be able to sense QS signals, potentially allowing them to alter QS outcomes. Recent experiments have established that eukaryotes have marked responses to the N-acyl l-homoserine lactone (AHL) signals used by Gram-negative bacteria for QS, and the responses of plants to AHLs have received considerable scrutiny to date. However, the molecular mechanisms by which plants, and eukaryotes in general, sense bacterial AHLs remain unclear. Herein, we report a systematic analysis of the responses of the model plants Arabidopsis thaliana and Medicago truncatula to a series of native AHLs and byproducts thereof. Our results establish that AHLs can significantly alter seedling growth in an acyl-chain length dependent manner. Based upon A. thaliana knockout studies and in vitro biochemical assays, we conclude that the observed growth effects are dependent upon AHL amidolysis by a plant-derived fatty acid amide hydrolase (FAAH) to yield l-homoserine. The accumulation of l-homoserine appears to encourage plant growth at low concentrations by stimulating transpiration, while higher concentrations inhibit growth by stimulating ethylene production. These results offer new insights into the mechanisms by which plant hosts can respond to QS signals and the potential role of QS in interkingdom associations.


ACS Chem. Biol., Article ASAP
DOI: 10.1021/cb500191a


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Balticidins A–D, Antifungal Hassallidin-Like Lipopeptides from the Baltic Sea Cyanobacterium Anabaena cylindrica Bio33

Balticidins A–D, Antifungal Hassallidin-Like Lipopeptides from the Baltic Sea Cyanobacterium Anabaena cylindrica Bio33 | Natural Products Chemistry Breaking News | Scoop.it

Balticidins A–D (14), four new antifungal lipopeptides, were isolated from the laboratory-cultivated cyanobacterium Anabaena cylindrica strain Bio33 isolated from a water sample collected from the Baltic Sea, Rügen Island, Germany. Fractionation of the 50% aqueous MeOH extract was performed by bioassay-guided silica gel column chromatography followed by SPE and repeated reversed-phase HPLC. The main fraction containing the compounds exhibited a strong and specific antifungal activity with inhibition zones in an agar-diffusion assay from 21 to 32 mm against Candida albicansCandida kruseiCandida maltosa,Aspergillus fumigatusMicrosporum gypseumMucor sp., and Microsporum canis. The structures were elucidated by multidimensional 1H and 13C NMR spectroscopy, HRESIMS, amino acid analysis, and sugar analysis. Spectroscopic data analysis afforded an unambiguous sequence of R.CHO(S1).CHOH.CONH-Thr(1)-Thr(2)-Thr(3)-HOTyr(4)-Dhb(5)-d-Gln(6)-Gly(7)-NMeThr(8)(S2)-l-Gln COOH(9), in which Dhb is dehydroaminobutyric acid, S1 is d(−)-arabinose-(3-1)-d-(+)-galacturonic acid, S2 is d-(+)-mannose, and R is the aliphatic residue -C13H26Cl or -C13H27. Besides NMeThr, d-allo-Thr, d-Thr, and l-Thr were identified, but the position of the enantiomers in the sequence is not clear. The four balticidins differ in their cyclic (24)/linear (13) core and the presence (12)/absence (34) of chlorine in the aliphatic unit.


J. Nat. Prod., Article ASAP
DOI: 10.1021/np401020a
Publication Date (Web): June 17, 2014




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