Natural Products Chemistry Breaking News
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Natural Products Chemistry Breaking News
A recompilation of news and links about natural products, organic chemistry and science more generally ...
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Selecting the Most Appropriate NMR Experiment to Access Weak and/or Very Long-Range Heteronuclear Correlations

Selecting the Most Appropriate NMR Experiment to Access Weak and/or Very Long-Range Heteronuclear Correlations | Natural Products Chemistry Breaking News | Scoop.it

Heteronuclear long-range NMR experiments are well established as essential NMR techniques for the structure elucidation of unknown natural products and small molecules. It is generally accepted that the absence of a given nJXH correlation in an HMBC or HSQMBC spectrum would automatically place the proton at least four bonds away from the carbon in question. This assumption can, however, be misleading in the case of a mismatch between the actual coupling constant and the delay used to optimize the experiment, which can lead to structural misassignments. Another scenario arises when an investigator, for whatever reason, needs to have access to very long-range correlations to confirm or refute a structure. In such cases, a conventional HMBC experiment will most likely fail to provide the requisite correlation, regardless of the delay optimization. Two recent methods for visualizing extremely weak or very long-range connectivities are the LR-HSQMBC and the HSQMBC-TOCSY experiments. Although they are intended to provide similar structural information, they utilize different transfer mechanisms, which differentiates the experiments, making each better suited for specific classes of compounds. In this report we have sought to examine the considerations implicit in choosing the best experiment to access weak or very long-range correlations for different types of molecules.

 

 
J. Nat. Prod., Article ASAP
DOI: 10.1021/acs.jnatprod.6b00139
Publication Date (Web): May 3, 2016
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Selecting the Most Appropriate NMR Experiment to Access Weak and/or Very Long-Range Heteronuclear Correlations

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The Chemical Ecology of Predatory Soil Bacteria

The Chemical Ecology of Predatory Soil Bacteria | Natural Products Chemistry Breaking News | Scoop.it

ClickThe study of natural products is entering a renaissance, driven by the discovery that the majority of bacterial secondary metabolites are not produced under standard laboratory conditions. Understanding the ecological role of natural products is key to efficiently directing our screening efforts, and to ensuring that each screen efficiently captures the full biosynthetic repertoire of the producing organisms. Myxobacteria represent one of the most common and diverse groups of bacteria, with roughly 2500 strains publically available. Fed largely through predation, the myxobacteria have developed a large repertoire of natural products that target other microorganisms, including bacteria and fungi. Many of these interactions can be observed in predation assays, providing direct evidence for environmental interactions. With a focus on Myxococcus xanthus, this review will highlight how recent advances in myxobacteria are revealing the chemical ecology of bacterial natural products.

 

Department of Chemistry and Biochemistry, Faculty of Arts and Science, Concordia University, Montreal, Quebec, Canada H4B 1R6
ACS Chem. Biol., Article ASAP
DOI: 10.1021/acschembio.6b00176
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War, peace & chemistry ... just under our feets.

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Metabolic engineering with systems biology tools to optimize production of prokaryotic secondary metabolites

Metabolic engineering with systems biology tools to optimize production of prokaryotic secondary metabolites | Natural Products Chemistry Breaking News | Scoop.it
Metabolic engineering using systems biology tools is increasingly applied to overproduce secondary metabolites for their potential industrial production. In this Highlight, recent relevant metabolic engineering studies are analyzed with emphasis on host selection and engineering approaches for the optimal production of various prokaryotic secondary metabolites: native versus heterologous hosts (e.g., Escherichia coli) and rational versus random approaches. This comparative analysis is followed by discussions on systems biology tools deployed in optimizing the production of secondary metabolites. The potential contributions of additional systems biology tools are also discussed in the context of current challenges encountered during optimization of secondary metabolite production.

 

 

Nat. Prod. Rep., 2016, Advance Article


DOI: 10.1039/C6NP00019C

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Metabolic engineering with systems biology tools to optimize production of prokaryotic secondary metabolites

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Improved batch correction in untargeted MS-based metabolomics

Improved batch correction in untargeted MS-based metabolomics | Natural Products Chemistry Breaking News | Scoop.it
Introduction

Batch effects in large untargeted metabolomics experiments are almost unavoidable, especially when sensitive detection techniques like mass spectrometry (MS) are employed. In order to obtain peak intensities that are comparable across all batches, corrections need to be performed. Since non-detects, i.e., signals with an intensity too low to be detected with certainty, are common in metabolomics studies, the batch correction methods need to take these into account.

Objectives

This paper aims to compare several batch correction methods, and investigates the effect of different strategies for handling non-detects.

Methods

Batch correction methods usually consist of regression models, possibly also accounting for trends within batches. To fit these models quality control samples (QCs), injected at regular intervals, can be used. Also study samples can be used, provided that the injection order is properly randomized. Normalization methods, not using information on batch labels or injection order, can correct for batch effects as well. Introducing two easy-to-use quality criteria, we assess the merits of these batch correction strategies using three large LC–MS and GC–MS data sets of samples from Arabidopsis thaliana.

Results

The three data sets have very different characteristics, leading to clearly distinct behaviour of the batch correction strategies studied. Explicit inclusion of information on batch and injection order in general leads to very good corrections; when enough QCs are available, also general normalization approaches perform well. Several approaches are shown to be able to handle non-detects—replacing them with very small numbers such as zero seems the worst of the approaches considered.

Conclusion

The use of quality control samples for batch correction leads to good results when enough QCs are available. If an experiment is properly set up, batch correction using the study samples usually leads to a similar high-quality correction, but has the advantage that more metabolites are corrected. The strategy for handling non-detects is important: choosing small values like zero can lead to suboptimal batch corrections.

KeywordsBatch correction Untargeted metabolomics Non-detects Mass spectrometry Arabidopsis thaliana
 
 
 
  • Ron Wehrens 
  • , Jos. A. Hageman
  • , Fred van Eeuwijk
  • , Rik Kooke
  • , Pádraic J. Flood
  • , Erik Wijnker
  • , Joost J. B. Keurentjes
  • , Arjen Lommen
  • , Henriëtte D. L. M. van Eekelen
    • , Robert D. Hall
    • , Roland Mumm
    • , Ric C. H. de Vos

 

Metabolomics

May 2016, 12:88

NatProdChem's insight:

Insights for a recurent problem in LC-MS based metabolomics

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Balakumaran Chandrasekar's curator insight, March 25, 9:47 AM

Insights for a recurent problem in LC-MS based metabolomics

Joseval Estigaribia's curator insight, March 31, 10:44 AM

Insights for a recurent problem in LC-MS based metabolomics

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Wewakazole B, a Cytotoxic Cyanobactin from the Cyanobacterium Moorea producens Collected in the Red Sea

Wewakazole B, a Cytotoxic Cyanobactin from the Cyanobacterium Moorea producens Collected in the Red Sea | Natural Products Chemistry Breaking News | Scoop.it

A mass spectrometry (MS)-guided isolation has led to the purification of a new cyanobactin, wewakazole B (1), along with the known compound curacin D from a Red Sea Moorea producens. The planar structure of 1 was elucidated using a combination of NMR and MS techniques. After ozonolysis and acid hydrolysis, the absolute configurations of the amino acid components of 1 were determined by chiral-phase LC-MS and HPLC analyses. Notably, compound 1 exhibited cytotoxic activity toward human MCF7 breast cancer cells (IC50 = 0.58 μM) and human H460 lung cancer cells (IC50 = 1.0 μM) and was also found to be inactive in a siderophore assay.

 

J. Nat. Prod., Article ASAP
DOI: 10.1021/acs.jnatprod.6b00051

 

NatProdChem's insight:

Wewakazole B, a Cytotoxic Cyanobactin from the Cyanobacterium Moorea producens Collected in the Red Sea

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Wewakazole B, a Cytotoxic Cyanobactin from the Cyanobacterium Moorea producens Collected in the Red Sea

Warwick Raverty's curator insight, March 18, 9:50 AM

Wewakazole B, a Cytotoxic Cyanobactin from the Cyanobacterium Moorea producens Collected in the Red Sea

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Wewakazole B, a Cytotoxic Cyanobactin from the Cyanobacterium Moorea producens Collected in the Red Sea

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Advances in identification and validation of protein targets of natural products without chemical modification - Natural Product Reports

Advances in identification and validation of protein targets of natural products without chemical modification - Natural Product Reports | Natural Products Chemistry Breaking News | Scoop.it

Identification of the target proteins of natural products is pivotal to understanding the mechanisms of action to develop natural products for use as molecular probes and potential therapeutic drugs. Affinity chromatography of immobilized natural products has been conventionally used to identify target proteins, and has yielded good results. However, this method has limitations, in that labeling or tagging for immobilization and affinity purification often result in reduced or altered activity of the natural product. New strategies have recently been developed and applied to identify the target proteins of natural products and synthetic small molecules without chemical modification of the natural product. These direct and indirect methods for target identification of label-free natural products include drug affinity responsive target stability (DARTS), stability of proteins from rates of oxidation (SPROX), cellular thermal shift assay (CETSA), thermal proteome profiling (TPP), and bioinformatics-based analysis of connectivity. This review focuses on and reports case studies of the latest advances in target protein identification methods for label-free natural products. The integration of newly developed technologies will provide new insights and highlight the value of natural products for use as biological probes and new drug candidates

 

J. Chang,a   Y. Kima and   H. J. Kwon*ab  
 
Nat. Prod. Rep., 2016, Advance Article

DOI: 10.1039/C5NP00107B
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Chemoreactive Natural Products that Afford Resistance Against Disparate Antibiotics and Toxins

Microorganisms use chemical inactivation strategies to circumvent toxicity caused by many types of antibiotics. Yet in all reported cases, this approach is limited to enzymatically facilitated mechanisms that each target narrow ranges of chemically related scaffolds. The fungus-derived shikimate analogues, pericoxide and pericosine A, were identified as chemoreactive natural products that attenuate the antagonistic effects of several synthetic and naturally derived antifungal agents. Experimental and computational studies suggest that pericoxide and pericosine A readily react via SN2′ mechanisms against a variety of nucleophilic substances under both in vitro aqueous and in situ co-culture conditions. Many of the substitution products from this reaction were highly stable and exhibited diminished toxicities against environmental fungal isolates, including the Tolypocladium sp. strain that produced pericoxide and pericosine A.

  1. Dr. Lin Du†,
  2. Dr. Jianlan You†,
  3. Prof. Dr. Kenneth M. Nicholas and
  4. Prof. Dr. Robert H. Cichewicz*

Article first published online: 1 MAR 2016

DOI: 10.1002/ange.201511348Very interesting

 

 

NatProdChem's insight:

Very interseting article by Cichewicz's team, were the role of a fungal secondary metabolite is explored in detail.

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Very interseting article by Cichewicz's team, were the role of a fungal secondary metabolite is explored in detail.

Joseval Estigaribia's curator insight, March 10, 8:54 AM

Very interseting article by Cichewicz's team, were the role of a fungal secondary metabolite is explored in detail.

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Fragmentation trees reloaded

Fragmentation trees reloaded | Natural Products Chemistry Breaking News | Scoop.it
Background

Untargeted metabolomics commonly uses liquid chromatography mass spectrometB¨ry to measure abundances of metabolites; subsequent tandem mass spectrometry is used to derive information about individual compounds. One of the bottlenecks in this experimental setup is the interpretation of fragmentation spectra to accurately and efficiently identify compounds. Fragmentation trees have become a powerful tool for the interpretation of tandem mass spectrometry data of small molecules. These trees are determined from the data using combinatorial optimization, and aim at explaining the experimental data via fragmentation cascades. Fragmentation tree computation does not require spectral or structural databases. To obtain biochemically meaningful trees, one needs an elaborate optimization function (scoring).

Results

We present a new scoring for computing fragmentation trees, transforming the combinatorial optimization into a Maximum A Posteriori estimator. We demonstrate the superiority of the new scoring for two tasks: both for the de novo identification of molecular formulas of unknown compounds, and for searching a database for structurally similar compounds, our method SIRIUS 3, performs significantly better than the previous version of our method, as well as other methods for this task.

Conclusion
SIRIUS 3 can be a part of an untargeted metabolomics workflow, allowing researchers to investigate unknowns using automated computational methods
 
    Sebastian BöckerEmail author and Kai Dührkop
Journal of Cheminformatics20168:5

DOI: 10.1186/s13321-016-0116-8

NatProdChem's insight:

Böcker's team release a the v.3 of SIRIUS ! Tough bioinformatics approaches for MS/MS data interpretation. FTs will here predict candidates structures with NO databases needed !

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Böcker's team release a the v.3 of SIRIUS ! Tough bioinformatics approaches for MS/MS data interpretation. FTs will here predict candidates structures with NO databases needed !

Joseval Estigaribia's curator insight, March 10, 8:59 AM

Böcker's team release a the v.3 of SIRIUS ! Tough bioinformatics approaches for MS/MS data interpretation. FTs will here predict candidates structures with NO databases needed !

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Aspterpenacids A and B, Two Sesterterpenoids from a Mangrove Endophytic Fungus Aspergillus terreus H010 - Organic Letters (ACS Publications)

Aspterpenacids A and B, Two Sesterterpenoids from a Mangrove Endophytic Fungus Aspergillus terreus H010 - Organic Letters (ACS Publications) | Natural Products Chemistry Breaking News | Scoop.it

TAspterpenacids A and B, Two Sesterterpenoids from a Mangrove Endophytic Fungus Aspergillus terreus H010wo new sesterterpenoids, aspterpenacids A (1) and B (2), with an unusual carbon skeleton of a 5/3/7/6/5 ring system were isolated from the mangrove endophytic fungus Aspergillus terreus H010. Their structures were elucidated on the basis of spectroscopic methods, single-crystal X-ray diffraction analysis, and electronic circular dichroism calculations. A biogenetic pathway for 1 and 2 is proposed. Both 1 and 2 showed no significant antibacterial activity or cytotoxicity at 50 μM.

 

Org. Lett., Article ASAP

DOI: 10.1021/acs.orglett.6b00336
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Aspterpenacids A and B, Two Sesterterpenoids from a Mangrove Endophytic Fungus Aspergillus terreus H010

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Aspterpenacids A and B, Two Sesterterpenoids from a Mangrove Endophytic Fungus Aspergillus terreus H010

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Aspterpenacids A and B, Two Sesterterpenoids from a Mangrove Endophytic Fungus Aspergillus terreus H010

Warwick Raverty's curator insight, March 8, 10:33 PM

Aspterpenacids A and B, Two Sesterterpenoids from a Mangrove Endophytic Fungus Aspergillus terreus H010

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Inhibition of Chikungunya Virus-Induced Cell Death by Salicylate-Derived Bryostatin Analogues Provides Additional Evidence for a PKC-Independent Pathway

Inhibition of Chikungunya Virus-Induced Cell Death by Salicylate-Derived Bryostatin Analogues Provides Additional Evidence for a PKC-Independent Pathway | Natural Products Chemistry Breaking News | Scoop.it

Chikungunya virus (CHIKV) has been spreading rapidly, with over one million confirmed or suspected cases in the Americas since late 2013. Infection with CHIKV causes devastating arthritic and arthralgic symptoms. Currently, there is no therapy to treat this disease, and the only medications focus on relief of symptoms. Recently, protein kinase C (PKC) modulators have been reported to inhibit CHIKV-induced cell death in cell assays. The salicylate-derived bryostatin analogues described here are structurally simplified PKC modulators that are more synthetically accessible than the natural product bryostatin 1, a PKC modulator and clinical lead for the treatment of cancer, Alzheimer’s disease, and HIV eradication. Evaluation of the anti-CHIKV activity of these salicylate-derived bryostatin analogues in cell culture indicates that they are among the most potent cell-protective agents reported to date. Given that they are more accessible and significantly more active than the parent natural product, they represent new therapeutic leads for controlling CHIKV infection. Significantly, these analogues also provide evidence for the involvement of a PKC-independent pathway. This adds a fundamentally distinct aspect to the importance or involvement of PKC modulation in inhibition of chikungunya virus replication, a topic of recent and growing interest.



J. Nat. Prod., Article ASAP
DOI: 10.1021/acs.jnatprod.5b01017
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Withanolide Structural Revisions by 13C NMR Spectroscopic Analysis Inclusive of the γ-Gauche Effect

Withanolide Structural Revisions by 13C NMR Spectroscopic Analysis Inclusive of the γ-Gauche Effect | Natural Products Chemistry Breaking News | Scoop.it

A classic withanolide is defined as a highly oxygenated C28 ergostane-type steroid that is characterized by a C22-hydroxy-C26-oic acid δ-lactone in the nine-carbon side chain. Analysis of the reported 13C NMR data of classic withanolides with hydroxy groups (C-14, C-17, and C-20) revealed that (1) a hydroxy (C-14 or C-17) substituent significantly alters the chemical shifts (C-7, C-9, C-12, and C-21) via the γ-gauche effect; (2) the chemical shift values (C-9, C-12, and C-21) reflect the orientation (α or β) of the hydroxy moiety (C-14 or C-17); (3) a double-bond positional change in ring A (Δ2 to Δ3), or hydroxylation (C-27), results in a minuscule effect on the chemical shifts of carbons in rings C and D (from C-12 to C-18); and (4) the 13C NMR γ-gauche effect method is more convenient and reliable than the traditional approach (1H NMR shift comparisons in C5D5N versus CDCl3) to probe the orientation of the hydroxy substituent (C-14 and C-17). Utilization of these rules demonstrated that the reported 13C NMR data of withanolides 1a29a were inconsistent with their published structures, which were subsequently revised as 116 and 12 and 1829, respectively. When combined, this strongly supports the application of these methods to determine the relative configuration of steroidal substituents.


Department of Medicinal Chemistry, University of Kansas, Lawrence, Kansas 66045, United States
J. Nat. Prod., Article ASAP
DOI: 10.1021/acs.jnatprod.5b00648
Publication Date (Web): February 19, 2016
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NMR is like your mother ... it allways tells you the truth ;)

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Rational and Efficient Preparative Isolation of Natural Products by MPLC-UV-ELSD based on HPLC to MPLC Gradient Transfer

Rational and Efficient Preparative Isolation of Natural Products by MPLC-UV-ELSD based on HPLC to MPLC Gradient Transfer | Natural Products Chemistry Breaking News | Scoop.it

« In natural product research, the isolation of biomarkers or bioactive compounds from complex natural extracts represents an essential step for de novo identification and bioactivity assessment. When pure natural products have to be obtained in milligram quantities, the chromatographic steps are generally labourious and time-consuming. In this respect, an efficient method has been developed for the reversed-phase gradient transfer from high-performance liquid chromatography to medium-performance liquid chromatography for the isolation of pure natural products at the level of tens of milligrams from complex crude natural extracts. The proposed method provides a rational way to predict retention behaviour and resolution at the analytical scale prior to medium-performance liquid chromatography, and guarantees similar performances at both analytical and preparative scales. The optimisation of the high-performance liquid chromatography separation and system characterisation allows for the prediction of the gradient at the medium-performance liquid chromatography scale by using identical stationary phase chemistries. The samples were introduced in medium-performance liquid chromatography using a pressure-resistant aluminium dry load cell especially designed for this study to allow high sample loading while maintaining a maximum achievable flow rate for the separation. The method has been validated with a mixture of eight natural product standards. Ultraviolet and evaporative light scattering detections were used in parallel for a comprehensive monitoring. In addition, post-chromatographic mass spectrometry detection was provided by high-throughput ultrahigh-performance liquid chromatography time-of-flight mass spectrometry analyses of all fractions. The processing of all liquid chromatography-mass spectrometry data in the form of an medium-performance liquid chromatography x ultra high-performance liquid chromatography time-of-flight mass spectrometry matrix enabled an efficient localisation of the compounds of interest in the generated fractions. The methodology was successfully applied for the separation of three different plant extracts that contain many diverse secondary metabolites. The advantages and limitations of this approach and the theoretical chromatographic background that rules such as liquid chromatography gradient transfer are presented from a practical viewpoint. »


Planta Med 2015; 81(17): 1636-1643
DOI: 10.1055/s-0035-1545912
Original Papers
Rational and Efficient Preparative Isolation of Natural Products by MPLC-UV-ELSD based on HPLC to MPLC Gradient Transfer
Soura Challal1, Emerson Ferreira Queiroz1, Benjamin Debrus1, Werner Kloeti1, Davy Guillarme1, Mahabir Prashad Gupta2, Jean-Luc Wolfender1
  • 1School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, Geneva, Switzerland
  • 2Center for Pharmacognostic Research on Panamanian Flora-CIFLORPAN, University of Panama, Panama, Republic of Panama


© 2016 Georg Thieme Verlag KG

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Biogeography of a human oral microbiome at the micron scale

Biogeography of a human oral microbiome at the micron scale | Natural Products Chemistry Breaking News | Scoop.it

The physiology and ecology of complex microbial communities are strongly dependent on the immediate surroundings of each microbe, including the identity of neighboring microbes; however, information on the micron-scale organization of microbiomes is largely lacking. Using sequencing data combined with spectral fluorescence imaging, we have discovered a multigenus, highly organized microbial consortium in human dental plaque. The spatial structure of the consortium reveals unanticipated interactions and provides a framework for understanding the organization, metabolism, and systems biology of the microbiome and ultimately, its effect on the health of the human host. Our synthesis of high-throughput sequencing data with spatial and structural information shows the informative value of microbial biogeography at the micron scale.


  1. Jessica L. Mark Welcha,b,1,
  2. Blair J. Rossettia,b,
  3. Christopher W. Riekenb,
  4. Floyd E. Dewhirsta,c, and
  5. Gary G. Borisya,b,1

PNAS,  E791–E800, doi: 10.1073/pnas.1522149113

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Starring microbial communities into the eyes

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Nitric Oxide Inhibitory Meroterpenoids from the Fungus Penicillium purpurogenum MHZ 111

Nitric Oxide Inhibitory Meroterpenoids from the Fungus Penicillium purpurogenum MHZ 111 | Natural Products Chemistry Breaking News | Scoop.it

Five new meroterpenoids, purpurogenolides A–E (15), and four known metabolites (69) were isolated from the solid substrate fermentation cultures of the fungus Penicillium purpurogenum MHz 111. The structures of the new meroterpenoids were elucidated by analysis of spectroscopic and spectrometric data (1D and 2D NMR, IR, and HRESIMS). The absolute configurations of 1 and 5 were determined by single-crystal X-ray crystallographic analysis, and those of 24 were elucidated on the basis of experimental and calculated electronic circular dichroism spectra. Compounds 24 and 6 showed inhibition of nitric oxide production in lipopolysaccharide-activated BV-2 microglial cells with IC50 values of 0.8–30.0 μM.

 

J. Nat. Prod., Article ASAP
DOI: 10.1021/acs.jnatprod.6b00160
Publication Date (Web): April 27, 2016
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Nitric Oxide Inhibitory Meroterpenoids from the Fungus Penicillium purpurogenum MHZ 111

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Ibogan, Aspidosperman, Vincamine, and Bisindole Alkaloids from a Malayan Tabernaemontana corymbosa: Iboga Alkaloids with C-20α Substitution

Ibogan, Aspidosperman, Vincamine, and Bisindole Alkaloids from a Malayan Tabernaemontana corymbosa: Iboga Alkaloids with C-20α Substitution | Natural Products Chemistry Breaking News | Scoop.it

Click here to Ten new indole alkaloids (110) comprising five ibogan, two aspidosperman, one vincamine, and two bisindole alkaloids, in addition to 32 known alkaloids, were isolated from the stem-bark extract of a Malayan Tabernaemontana corymbosa. The structures of these alkaloids were determined based on analysis of the NMR and MS data and, in five instances (1, 3, 5, 6, 8), confirmed by X-ray diffraction analysis. Two of the iboga alkaloids, conodusines B (2) and C (3), and the iboga-containing bisindole tabernamidine B (10) are notable for the presence of an α-substituted acetyl group at C-20 of the iboga carbon skeleton. The iboga alkaloid (+)-conodusine E (5) had MS and NMR data that were identical to those of (−)-ervatamine I, recently isolated from Ervatamia hainanensis. Establishment of the absolute configuration of (+)-conodusine E (5) was based on analysis of the ECD data, correlation with (−)-heyneanine, and X-ray analysis, which showed that (+)-5 belongs to the same enantiomeric series as exemplified by (−)-coronaridine. The configuration at C-20′ of the previously reported Tabernaemontana bisindole alkaloid 19′-oxotabernamine (renamed tabernamidine B) required revision based on the present results. Several of the bisindoles showed pronounced in vitro growth inhibitory activity against drug-sensitive and vincristine-resistant KB cells.

 

Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia
J. Nat. Prod., Article ASAP
DOI: 10.1021/acs.jnatprod.6b00129
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Variochelins, Lipopeptide Siderophores from Variovorax boronicumulans Discovered by Genome Mining

Variochelins, Lipopeptide Siderophores from Variovorax boronicumulans Discovered by Genome Mining | Natural Products Chemistry Breaking News | Scoop.it

Photoreactive siderophores have a major impact on the growth of planktonic organisms. To date, these molecules have mainly been reported from marine bacteria, although evidence is now accumulating that some terrestrial bacteria also harbor the biosynthetic potential for their production. In this paper, we describe the genomics-driven discovery and characterization of variochelins, lipopeptide siderophores from the bacterium Variovorax boronicumulans, which thrives in soil and freshwater habitats. Variochelins are different from most other lipopeptide siderophores in that their biosynthesis involves a polyketide synthase. We demonstrate that the ferric iron complex of variochelin A possesses photoreactive properties and present the MS-derived structures of two degradation products that emerge upon light exposure.

 

J. Nat. Prod., Article ASAP
DOI: 10.1021/acs.jnatprod.5b00932
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Variochelins, Lipopeptide Siderophores from Variovorax boronicumulans Discovered by Genome Mining

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Variochelins, Lipopeptide Siderophores from Variovorax boronicumulans Discovered by Genome Mining

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Deep Subseafloor Fungi as an Untapped Reservoir of Amphipathic Antimicrobial Compounds

Deep Subseafloor Fungi as an Untapped Reservoir of Amphipathic Antimicrobial Compounds | Natural Products Chemistry Breaking News | Scoop.it
The evolving global threat of antimicrobial resistance requires a deep renewal of the antibiotic arsenal including the isolation and characterization of new drugs. Underexplored marine ecosystems may represent an untapped reservoir of novel bioactive molecules. Deep-sea fungi isolated from a record-depth sediment core of almost 2000 m below the seafloor were investigated for antimicrobial activities. This antimicrobial screening, using 16 microbial targets, revealed 33% of filamentous fungi synthesizing bioactive compounds with activities against pathogenic bacteria and fungi. Interestingly, occurrence of antimicrobial producing isolates was well correlated with the complexity of the habitat (in term of microbial richness), as higher antimicrobial activities were obtained at specific layers of the sediment core. It clearly highlights complex deep-sea habitats as chemical battlefields where synthesis of numerous bioactive compounds appears critical for microbial competition. The six most promising deep subseafloor fungal isolates were selected for the production and extraction of bioactive compounds. Depending on the fungal isolates, antimicrobial compounds were only biosynthesized in semi-liquid or solid-state conditions as no antimicrobial activities were ever detected using liquid fermentation. An exception was made for one fungal isolate, and the extraction procedure designed to extract amphipathic compounds was successful and highlighted the amphiphilic profile of the bioactive metabolites.

 

Marion Navarri, Camille Jégou, Laurence Meslet-Cladière, Benjamin Brillet, Georges Barbier, Gaëtan Burgaudand Yannick Fleury *

Mar. Drugs 2016, 14(3), 50; doi:10.3390/md14030050
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Deep Subseafloor Fungi as an Untapped Reservoir of Amphipathic Antimicrobial Compounds
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Deep Subseafloor Fungi as an Untapped Reservoir of Amphipathic Antimicrobial Compounds
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Deep Subseafloor Fungi as an Untapped Reservoir of Amphipathic Antimicrobial Compounds
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Deep Subseafloor Fungi as an Untapped Reservoir of Amphipathic Antimicrobial Compounds
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Grisemycin, a Bridged Angucyclinone with a Methylsulfinyl Moiety from a Marine-Derived Streptomyces sp.

Grisemycin, a Bridged Angucyclinone with a Methylsulfinyl Moiety from a Marine-Derived Streptomyces sp. | Natural Products Chemistry Breaking News | Scoop.it

Grisemycin (1), the first sulfur angucyclinone with an unusual ether-bridged system, was isolated from a marine-derived Streptomyces griseus strain M268. Its novel, here cage-like, structure was determined by spectroscopic analysis and single-crystal X-ray diffraction. Compound 1 exhibited modestly selective activity against the HL-60 cell line with an IC50 value of 31.54 μM. Futhermore, the absolute stereochemistry of kiamycin (2), an 1,12-epoxybenz[a]anthracene, previously obtained from the same strain, was established by X-ray diffraction analysis.

 

 
Org. Lett., Article ASAP
DOI: 10.1021/acs.orglett.6b00332
Publication Date (Web): March 9, 2016

 

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Chilenopeptins A and B, Peptaibols from the Chilean Sepedonium aff. chalcipori KSH 883

Chilenopeptins A and B, Peptaibols from the Chilean Sepedonium aff. chalcipori KSH 883 | Natural Products Chemistry Breaking News | Scoop.it

The Chilean Sepedonium aff. chalcipori strain KSH 883, isolated from the endemic Boletus loyo Philippi, was studied in a polythetic approach based on chemical, molecular, and biological data. A taxonomic study of the strain using molecular data of the ITS, EF1-α, and RPB2 barcoding genes confirmed the position of the isolated strain within the S. chalcipori clade, but also suggested the separation of this clade into three different species. Two new linear 15-residue peptaibols, named chilenopeptins A (1) and B (2), together with the known peptaibols tylopeptins A (3) and B (4) were isolated from the semisolid culture of strain KSH 883. The structures of 1 and 2 were elucidated on the basis of HRESIMSn experiments in conjunction with comprehensive 1D and 2D NMR analysis. Thus, the sequence of chilenopeptin A (1) was identified as Ac-Aib1-Ser2-Trp3-Aib4-Pro5-Leu6-Aib7-Aib8-Gln9-Aib10-Aib11-Gln12-Aib13-Leu14-Pheol15, while chilenopeptin B (2) differs from 1 by the replacement of Trp3 by Phe3. Additionally, the total synthesis of 1 and 2 was accomplished by a solid-phase approach, confirming the absolute configuration of all chiral amino acids as l. Both the chilenopeptins (1 and 2) and tylopeptins (3 and 4) were evaluated for their potential to inhibit the growth of phytopathogenic organisms.

 

 

 
J. Nat. Prod., Article ASAP
DOI: 10.1021/acs.jnatprod.5b01018
Publication Date (Web): March 8, 2016

 

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Variability in the carbon isotope composition of individual amino acids in plant proteins from different sources: 1 Leaves

Variability in the carbon isotope composition of individual amino acids in plant proteins from different sources: 1 Leaves | Natural Products Chemistry Breaking News | Scoop.it
Abstract The natural carbon isotope composition of individual amino acids from plant leaf proteins has been measured to establish potential sources of variability.
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Identification of Thiotetronic Acid Antibiotic Biosynthetic Pathways by Target-directed Genome Mining

Identification of Thiotetronic Acid Antibiotic Biosynthetic Pathways by Target-directed Genome Mining | Natural Products Chemistry Breaking News | Scoop.it
Recent genome sequencing efforts have led to the rapid accumulation of uncharacterized or “orphaned” secondary metabolic biosynthesis gene clusters (BGCs) in public databases. This increase in DNA-sequenced big data has given rise to significant challenges in the applied field of natural product genome mining, including (i) how to prioritize the characterization of orphan BGCs and (ii) how to rapidly connect genes to biosynthesized small molecules. Here, we show that by correlating putative antibiotic resistance genes that encode target-modified proteins with orphan BGCs, we predict the biological function of pathway specific small molecules before they have been revealed in a process we call target-directed genome mining. By querying the pan-genome of 86 Salinispora bacterial genomes for duplicated house-keeping genes colocalized with natural product BGCs, we prioritized an orphan polyketide synthase-nonribosomal peptide synthetase hybrid BGC (tlm) with a putative fatty acid synthase resistance gene. We employed a new synthetic double-stranded DNA-mediated cloning strategy based on transformation-associated recombination to efficiently capture tlm and the related ttm BGCs directly from genomic DNA and to heterologously express them in Streptomyces hosts. We show the production of a group of unusual thiotetronic acid natural products, including the well-known fatty acid synthase inhibitor thiolactomycin that was first described over 30 years ago, yet never at the genetic level in regards to biosynthesis and autoresistance. This finding not only validates the target-directed genome mining strategy for the discovery of antibiotic producing gene clusters without a priori knowledge of the molecule synthesized but also paves the way for the investigation of novel enzymology involved in thiotetronic acid natural product biosynthesis.

 

† Scripps Institution of Oceanography, University of California, San Diego, La Jolla, California, United States
‡ Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, United States
§ Centro de Genómica y Bioinformática, Facultad de Ciencias, Universidad Mayor, Campus Huechuraba, Camino a la Pirámide 5750, Santiago, Chile
ACS Chem. Biol., 2015, 10 (12), pp 2841–2849
DOI: 10.1021/acschembio.5b00658
Publication Date (Web): October 12, 2015
NatProdChem's insight:

Genome miners strike again !

 

Identification of Thiotetronic Acid Antibiotic Biosynthetic Pathways by Target-directed Genome Mining

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Balakumaran Chandrasekar's curator insight, March 9, 5:53 AM

Genome miners strike again !

 

Identification of Thiotetronic Acid Antibiotic Biosynthetic Pathways by Target-directed Genome Mining

Joseval Estigaribia's curator insight, March 10, 9:00 AM

Genome miners strike again !

 

Identification of Thiotetronic Acid Antibiotic Biosynthetic Pathways by Target-directed Genome Mining

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Integration of Molecular Networking and In-Silico MS/MS Fragmentation for Natural Products Dereplication

Integration of Molecular Networking and In-Silico MS/MS Fragmentation for Natural Products Dereplication | Natural Products Chemistry Breaking News | Scoop.it

Dereplication represents a key step for rapidly identifying known secondary metabolites in complex biological matrices. In this context, liquid-chromatography coupled to high resolution mass spectrometry (LC-HRMS) is increasingly used and, via untargeted data-dependent MS/MS experiments, massive amounts of detailed information on the chemical composition of crude extracts can be generated. An efficient exploitation of such data sets requires automated data treatment and access to dedicated fragmentation databases. Various novel bioinformatics approaches such as molecular networking (MN) and in-silico fragmentation tools have emerged recently and provide new perspective for early metabolite identification in natural products (NPs) research. Here we propose an innovative dereplication strategy based on the combination of MN with an extensive in-silico MS/MS fragmentation database of NPs. Using two case studies, we demonstrate that this combined approach offers a powerful tool to navigate through the chemistry of complex NPs extracts, dereplicate metabolites, and annotate analogues of database entries.

 

Anal. Chem., Article ASAP
DOI: 10.1021/acs.analchem.5b04804
Publication Date (Web): February 16, 2016
NatProdChem's insight:

New strategy for natural products dereplication ! It's all here : http://oolonek.github.io/ISDB/

 

 
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Institut de Chimie des Substances Naturelles - Marc Litaudon lauréat 2016 de la médaille de cristal du CNRS

Institut de Chimie des Substances Naturelles - Marc Litaudon lauréat 2016 de la médaille de cristal du CNRS | Natural Products Chemistry Breaking News | Scoop.it
Au cours de ces travaux, il a notamment isolé, à partir de 125 kg de foies et viscères de murènes, 350 µg de ciguatoxine (toxine de type polyéther d’environ 1200 de poids moléculaire responsable de l’intoxication ciguatérique ou "ciguatera" causant des troubles digestifs, neurologiques et cardio-vasculaires pouvant être graves). La ciguatoxine a été obtenue avec une pureté de l’ordre de 95%, ce qui a permis au Prof. T. Yasumoto d’en déterminer la structure et sa configuration (1989 et 1990).
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Well deserved prize for a great natural products chemist and a great person !

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Natural products discovery needs improved taxonomic and geographic information - Natural Product Reports (RSC Publishing)

Natural products discovery needs improved taxonomic and geographic information - Natural Product Reports (RSC Publishing) | Natural Products Chemistry Breaking News | Scoop.it

Marine and terrestrial organisms yield a remarkable chemical diversity and are important sources for discovery of new chemical products. In order to maximize the bioprospecting efficiency of natural products (NP), taxonomy, geography and biodiversity are starting to be used to draw conclusions on which taxonomic groups and/or regions may be of interest for future research. However, accurate taxonomic information and sampling location of source organisms have often been overlooked. Although these issues were already reported a few decades ago and improvements have been made, such outstanding problems are still recurrent in recent peer-reviewed literature. Here, we focus on the importance of taxonomic and geographic identification of source material and illustrate how taxonomic and geographic data of source organisms continues to be poorly handled. It is our opinion that this issue needs to be discussed within the NP community with the ultimate goal of improving publication standards and guaranteeing the scientific principle of research reproducibility. Moreover, by doing so, it will be possible to take advantage of information available in the literature to develop cross-disciplinary meta-analyses that may help to advance the state of the art of NP research and future bioprospecting endeavours.


Nat. Prod. Rep., 2016, Advance Article


DOI: 10.1039/C5NP00130G



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Don't forget you GPS in your next field collection !

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3-Acylated tetramic and tetronic acids as natural metal binders: myth or reality?

3-Acylated tetramic and tetronic acids as natural metal binders: myth or reality? | Natural Products Chemistry Breaking News | Scoop.it

3-Acylated tetramic and tetronic acids are characterized by a low pKa and are likely to be deprotonated under physiological conditions. In addition, their structure makes them excellent chelators of metallic cations. We will discuss the significance of these chemical properties with regard to the biological properties and mechanisms of action of these compounds, highlighting the importance of considering them as salts or chelates for biological purposes, rather than acids.


Nat. Prod. Rep., 2016, Advance Article


DOI: 10.1039/C5NP00144G


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