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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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New insights into the echinocandins and other fungal non-ribosomal peptides and peptaibiotics

New insights into the echinocandins and other fungal non-ribosomal peptides and peptaibiotics | Natural Products Chemistry Breaking News | Scoop.it

Non-ribosomal peptide synthetases (NRPSs) are a primary modality for fungal peptidic natural product assembly and are responsible for some of the best known, most useful, and most destructive fungal metabolites. Through genome sequencing and computer-assisted recognition of modular motifs of catalytic domains, one can now confidently identify most NRPS biosynthetic genes of a fungal strain. The biosynthetic gene clusters responsible for two of the most important classes of NRP fungal derived drugs, cyclosporine and the echinocandins, have been recently characterized by genomic sequencing and annotation. Complete biosynthetic gene clusters for the pneumocandins and echinocandins have been mapped at the genetic level and functionally characterized to some extent. Genomic sequencing of representative strains of most of the variants in the echinocandin family, including the wild-type of the three fungal strains employed for industrial-scale production of caspofungin, micafungin and anidulofungin, has enabled characterization of the basic architecture of the echinocandin NRPS pathways. A comparative analysis of how pathway genes cause variations in lipoinitiation, biosynthesis of the non-proteinogenic amino acids, amino acid substitutions, and hydroxylations and sulfonations of the core peptide and contribute to the molecular diversity of the family is presented. We also review new information on the natural functions of NRPs, the differences between fungal and bacterial NRPSs, and functional characterization of selected NRPS gene clusters. Continuing discovery of the new fungal nonribosomal peptides has contributed new structural diversity and potential insights into their biological functions among other natural peptides and peptaibiotics. We therefore provide an update on new peptides, depsipeptides and peptaibols discovered in the Fungi since 2009


Gerald Bills,*a   Yan Li,a   Li Chen,a   Qun Yue,a   Xue-Mei Niuab and  Zhiqiang Ana  
Show Affiliations
Nat. Prod. Rep., 2014, Advance Article


DOI: 10.1039/C4NP00046C


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Targeted Capture and Heterologous Expression of the Pseudoalteromonas Alterochromide Gene Cluster in Escherichia coli Represents a Promising Natural Product Exploratory Platform

Targeted Capture and Heterologous Expression of the Pseudoalteromonas Alterochromide Gene Cluster in Escherichia coli Represents a Promising Natural Product Exploratory Platform | Natural Products Chemistry Breaking News | Scoop.it

Marine pseudoalteromonads represent a very promising source of biologically important natural product molecules. To access and exploit the full chemical capacity of these cosmopolitan Gram-(–) bacteria, we sought to apply universal synthetic biology tools to capture, refactor and express biosynthetic gene clusters for the production of complex organic compounds in reliable host organisms. Here we report a platform for the capture of proteobacterial gene clusters using a Transformation-Associated Recombination (TAR) strategy coupled with direct pathway manipulation and expression in Escherichia coli. The ~34 kb pathway for production of alterochromide lipopeptides by Pseudoalteromonas piscicidaJCM 20779 was captured and heterologously expressed in E. coli utilizing native and E. coli-based T7 promoter sequences. Our approach enabled both facile production of the alterochromides and in vivo interrogation of gene function associated with alterochromide’s unusual brominated lipid side chain. This platform represents a simple but effective strategy for the discovery and biosynthetic characterization of natural products from marine proteobacteria.


ACS Synth. Biol., Just Accepted Manuscript
DOI: 10.1021/sb500280q
Publication Date (Web): August 20, 2014



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Belizentrin, a Highly Bioactive Macrocycle from the Dinoflagellate Prorocentrum belizeanum

Belizentrin, a Highly Bioactive Macrocycle from the Dinoflagellate Prorocentrum belizeanum | Natural Products Chemistry Breaking News | Scoop.it

Belizentrin (1), a novel 25-membered polyketide-derived macrocycle, was isolated from cultures of the marine dinoflagellate Prorocentrum belizeanum. This metabolite is the first member of an unprecedented class of polyunsaturated and polyhydroxylated macrolactams. The structure of 1 was primarily determined by NMR and computational methods. Pharmacological assays with cerebellar cells showed that 1 produces important changes in neuronal network integrity at nanomolar concentrations.


Org. Lett., Article ASAP
DOI: 10.1021/ol502102f
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Fungal siderophore metabolism with a focus on Aspergillus fumigatus

Fungal siderophore metabolism with a focus on Aspergillus fumigatus | Natural Products Chemistry Breaking News | Scoop.it

Siderophores are chelators synthesized by microbes to sequester iron. This article summarizes the knowledge on the fungal siderophore metabolism with a focus on Aspergillus fumigatus. In recent years, A. fumigatus became a role model for fungal biosynthesis, uptake and degradation of siderophores as well as regulation of siderophore-mediated iron handling and the elucidation of siderophore functions. Siderophore functions comprise uptake, intracellular transport and storage of iron. This proved to be crucial not only for adaptation to iron starvation conditions but also for germination, asexual and sexual propagation, antioxidative defense, mutual interaction, microbial competition as well as virulence in plant and animal hosts. Recent studies also indicate the high potential of siderophores and its biosynthetic pathway to improve diagnosis and therapy of fungal infections.


Show Affiliations
Nat. Prod. Rep., 2014, Advance Article


DOI: 10.1039/C4NP00071D
Received 30 May 2014, First published online 20 Aug 2014

NatProdChem's insight:

Fascinating natural product class. 


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Zebrafish-bioassay guided microfractionation identifies anticonvulsant steroid glycosides from the Philippine medicinal plant Solanum torvum

Zebrafish-bioassay guided microfractionation identifies anticonvulsant steroid glycosides from the Philippine medicinal plant Solanum torvum | Natural Products Chemistry Breaking News | Scoop.it

Medicinal plants used for the treatment of epilepsy are potentially a valuable source of novel anti-epileptic small molecules. To identify anticonvulsant secondary metabolites, we performed an in vivo, zebrafish-based screen of medicinal plants used in Southeast Asia for the treatment of seizures. Solanum torvum Sw. (Solanaceae) was identified as having significant anticonvulsant activity in zebrafish larvae with seizures induced by the GABAA antagonist pentylenetetrazol (PTZ). This finding correlates well with the ethnomedical use of this plant in the Philippines, where a water decoction of S. torvum leaves is used to treat epileptic seizures. HPLC microfractionation of the bioactive crude extract, in combination with the in vivo zebrafish seizure assay, enabled the rapid localization of several bioactive compounds that were partially identified on-line by UHPLC-TOF-MS as steroid glycosides. Targeted isolation of the active constituents from the methanolic extract enabled the complete de novo structure identification of the six main bioactive compounds that were also present in the traditional preparation. To partially mimic the in vivo metabolism of these triterpene glycosides, their common aglycone was generated by acid hydrolysis. The isolated molecules exhibited significant anticonvulsant activity in zebrafish seizure assays. These results underscore the potential of zebrafish bioassay-guided microfractionation to rapidly identify novel bioactive small molecules of natural origin.


Soura Challal , Olivia Erin M. Buenafe , Emerson Ferreira Queiroz , Snezana Maljevic , Laurence Marcourt , Merle Bock , Werner Kloeti , Fabian Millar Dayrit , Alan L. Harvey , Holger Lerche , Camila V. Esguerra , Peter A.M. de Witte , Jean-Luc Wolfender , and Alexander D Crawford


ACS Chem. Neurosci., Just Accepted Manuscript
DOI: 10.1021/cn5001342
Publication Date (Web): August 15, 2014
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A Generic Multiple Reaction Monitoring Based Approach for Plant Flavonoids Profiling Using a Triple Quadrupole Linear Ion Trap Mass Spectrometry - Springer

A Generic Multiple Reaction Monitoring Based Approach for Plant Flavonoids Profiling Using a Triple Quadrupole Linear Ion Trap Mass Spectrometry - Springer | Natural Products Chemistry Breaking News | Scoop.it

Flavonoids are one of the largest classes of plant secondary metabolites serving a variety of functions in plants and associating with a number of health benefits for humans. Typically, they are co-identified with many other secondary metabolites using untargeted metabolomics. The limited data quality of untargeted workflow calls for a shift from the breadth-first to the depth-first screening strategy when a specific biosynthetic pathway is focused on. Here we introduce a generic multiple reaction monitoring (MRM)-based approach for flavonoids profiling in plants using a hybrid triple quadrupole linear ion trap (QTrap) mass spectrometer. The approach includes four steps: (1) preliminary profiling of major aglycones by multiple ion monitoring triggered enhanced product ion scan (MIM-EPI); (2) glycones profiling by precursor ion triggered EPI scan (PI-EPI) of major aglycones; (3) comprehensive aglycones profiling by combining MIM-EPI and neutral loss triggered EPI scan (NL-EPI) of major glycone; (4) in-depth flavonoids profiling by MRM-EPI with elaborated MRM transitions. Particularly, incorporation of the NH3 loss and sugar elimination proved to be very informative and confirmative for flavonoids screening. This approach was applied for profiling flavonoids in Astragali radix (Huangqi), a famous herb widely used for medicinal and nutritional purposes in China. In total, 421 flavonoids were tentatively characterized, among which less than 40 have been previously reported in this medicinal plant. This MRM-based approach provides versatility and sensitivity that required for flavonoids profiling in plants and serves as a useful tool for plant metabolomics.

NatProdChem's insight:

421 flavonoids detected in Astragali radix !

LF

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NRPquest: Coupling Mass Spectrometry and Genome Mining for Nonribosomal Peptide Discovery

NRPquest: Coupling Mass Spectrometry and Genome Mining for Nonribosomal Peptide Discovery | Natural Products Chemistry Breaking News | Scoop.it

Nonribosomal peptides (NRPs) such as vancomycin and daptomycin are among the most effective antibiotics. While NRPs are biomedically important, the computational techniques for sequencing these peptides are still in their infancy. The recent emergence of mass spectrometry techniques for NRP analysis (capable of sequencing an NRP from small amounts of nonpurified material) revealed an enormous diversity of NRPs. However, as many NRPs have nonlinear structure (e.g., cyclic or branched-cyclic peptides), the standard de novo sequencing tools (developed for linear peptides) are not applicable to NRP analysis. Here, we introduce the first NRP identification algorithm, NRPquest, that performs mutation-tolerant and modification-tolerant searches of spectral data sets against a database of putative NRPs. In contrast to previous studies aimed at NRP discovery (that usually report very few NRPs), NRPquest revealed nearly a hundred NRPs (including unknown variants of previously known peptides) in a single study. This result indicates that NRPquest can potentially make MS-based NRP identification as robust as the identification of linear peptides in traditional proteomics.


J. Nat. Prod., Article ASAP
DOI: 10.1021/np500370c
Publication Date (Web): August 12, 2014


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Prenylated Indole Diketopiperazines from the Marine-Derived Fungus Aspergillus versicolor - The Journal of Organic Chemistry

Prenylated Indole Diketopiperazines from the Marine-Derived Fungus Aspergillus versicolor - The Journal of Organic Chemistry | Natural Products Chemistry Breaking News | Scoop.it

Jixing Peng Huquan Gao Jing Li Jing Ai ,Meiyu Geng Guojian Zhang Tianjiao Zhu ,Qianqun Gu , and Dehai Li *

DOI: 10.1021/jo5010179

Seven new prenylated indole diketopiperazines, versicamides A–G (17) and a novel chemical derivative from 7, versicamide H (8), along with three known analogic diketopiperazines (911) were obtained from the marine-derived fungus Aspergillus versicolorHDN08-60. Their structures were determined by spectroscopic techniques, including 2D NMR, ECD calculations, and single-crystal X-ray diffraction analysis, together with the assistance of further chemical conversions. The cytotoxicities of 18 were tested against the HeLa, HCT-116, HL-60, and K562 cell lines, but only 8 exhibited moderate activity against HL-60 cells, with an IC50 value of 8.7 μM. Further investigation with target screening showed that 8 exhibited selective PTK inhibitory activities.

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Emerging mass spectrometry techniques for the direct analysis of microbial colonies

Emerging mass spectrometry techniques for the direct analysis of microbial colonies | Natural Products Chemistry Breaking News | Scoop.it

Mass spectrometry techniques are powerful tools in studying specialized metabolites production from microbial colonies.

Direct analysis of microbial colonies can be used for clinical strain identification.

Microbial imaging mass spectrometry is able to visualize surface and secreted metabolites from microbial colonies.

Real-time mass spectrometry techniques enable the direct mass spectrometric interrogation of living microbial colonies.

•         Tandem mass spectrometry based molecular networking and emerging algorithms enable global molecular analysis of microbial metabolites.
DOI: 10.1016/j.mib.2014.06.014

Volume 19, June 2014, Pages 120–129


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From the Human Genome to the Human Proteome - 2014 - Angewandte Chemie International Edition

From the Human Genome to the Human Proteome - 2014 - Angewandte Chemie International Edition | Natural Products Chemistry Breaking News | Scoop.it
  1. Dr. Javier Muñoz2,* and
  2. Prof. Dr. Albert J. R. Heck1,*


DOI: 10.1002/anie.201406545

A herculean task: Determining the human proteome sets the ultimate challenge in cell biology as it is thought to consist of more than 1 000 000 proteoforms, in contrast to “only” 20 000 protein-coding genes. Two teams of researchers have now proved the translation of 18 000 proteins (and more than 27 000 isoforms) by mass spectrometry. They obtained important information on the extent of protein translation and alternative splicing.

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Microbial biosynthesis of medicinally important plant secondary metabolites - Natural Product Reports

Microbial biosynthesis of medicinally important plant secondary metabolites - Natural Product Reports | Natural Products Chemistry Breaking News | Scoop.it

Secondary metabolites derived from plants are a valuable source of pharmaceuticals, nutraceuticals, and cosmetics. To harness the potential of these natural products, reliable methods must be developed for their rapid and sustainable resupply. Microbial production of plant secondary metabolites through the heterologous expression of plant biosynthetic genes represents one such solution. This highlight focuses on recent advances in the microbial biosynthesis of plant secondary metabolites including terpenoids, flavonoids, and alkaloids as well as providing a brief insight into the current limitations and future prospects.


Show Affiliations
Nat. Prod. Rep., 2014, Advance Article


DOI: 10.1039/C4NP00057A





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8 Tips to Improve Your Pipetting Technique

8 Tips to Improve Your Pipetting Technique | Natural Products Chemistry Breaking News | Scoop.it

Learn new ways to improve the way you perform pipetting tasks in your lab. 

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Directly Decoupled Diffusion-Ordered NMR Spectroscopy for the Analysis of Compound Mixtures - Glanzer - 2014 - Chemistry - A European Journal -

Directly Decoupled Diffusion-Ordered NMR Spectroscopy for the Analysis of Compound Mixtures - Glanzer - 2014 - Chemistry - A European Journal - | Natural Products Chemistry Breaking News | Scoop.it
  1. Simon Glanzer and
  2. Prof. Dr. Klaus Zangger*

DOI: 10.1002/chem.201402920

For the analysis of compound mixtures by NMR spectroscopy, it is important to assign the different peaks to the individual constituents. Diffusion-ordered spectroscopy (DOSY) is often used for the separation of signals based on their self-diffusion coefficient. However, this method often fails in the case of signal overlap, which is a particular problem for 1H-detected DOSY spectra. Herein, an approach that allows the acquisition of homonuclear broadband-decoupled DOSY spectra without the introduction of an additional decoupling dimension, by instant decoupling during acquisition, is presented. It was demonstrated on a mixture of six alcohols, and the investigation of the binding of a dodecapeptide to membrane mimetics.

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Nature's Poisons

Nature's Poisons | Natural Products Chemistry Breaking News | Scoop.it
Mother nature is out to get us
NatProdChem's insight:

A nice blog with little stories about the little tricks nature has developed to protect itself from itself. It is written by a Justin Browers, a forensics toxicologist, and it is filled with a lot of anecdotes. A blog you may love to add to your RSS feed.


J.

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Urupocidin A: A New, Inducing iNOS Expression Bicyclic Guanidine Alkaloid from the Marine Sponge Monanchora pulchra

Urupocidin A: A New, Inducing iNOS Expression Bicyclic Guanidine Alkaloid from the Marine Sponge Monanchora pulchra | Natural Products Chemistry Breaking News | Scoop.it

Urupocidins A and B (1 and 2), bisguanidine alkaloids with an unprecedented skeleton system, derived from polyketide precursors and containing an unusual N-alkyl-N-hydroxyguanidine moiety, have been isolated from the sponge Monanhora pulchra. The structures of 1 and 2, including absolute configuration, were established using the detailed analysis of 1D and 2D NMR, CD, and mass spectra as well as chemical transformations. Compound 1 increases nitric oxide production in murine macrophages via inducing iNOS expression.


Org. Lett., 2014, 16 (16), pp 4292–4295
DOI: 10.1021/ol502013f
Publication Date (Web): August 5, 2014
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Discovering the secondary metabolite potential encoded within entomopathogenic fungi

Discovering the secondary metabolite potential encoded within entomopathogenic fungi | Natural Products Chemistry Breaking News | Scoop.it

This highlight discusses the secondary metabolite potential of the insect pathogens Metarhiziumand Beauveria, including a bioinformatics analysis of secondary metabolite genes for which no products are yet identified.


Show Affiliations
Nat. Prod. Rep., 2014, Advance Article


DOI: 10.1039/C4NP00054D



NatProdChem's insight:

Continuing this special "Fungal NPR issue" with evil entomopathogens Beauveria  sp.

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Spatial and temporal control of fungal natural product synthesis

Spatial and temporal control of fungal natural product synthesis | Natural Products Chemistry Breaking News | Scoop.it

Despite their oftentimes-elusive ecological role, fungal natural products have, for better or worse, impacted our daily lives tremendously owing to their diverse and potent bioactive properties. This Janus-faced nature of fungal natural products inevitably ushered in a field of research dedicated towards understanding the ecology, organisms, genes, enzymes, and biosynthetic pathways that give rise to this arsenal of diverse and complex chemistry. Ongoing research in fungal secondary metabolism has not only increased our appreciation for fungal natural products as an asset but also sheds light on the pivotal role that these once-regarded “metabolic wastes” play in fungal biology, defense, and stress response in addition to their potential contributions towards human mycoses. Full orchestration of secondary metabolism requires not only the seamless coordination between temporal and spatial control of SM-associated machineries (e.g. enzymes, cofactors, intermediates, and end-products) but also integration of these machineries into primary metabolic processes and established cellular mechanisms. An intriguing, but little known aspect of microbial natural product synthesis lies in the spatial organization of both pathway intermediates and enzymes responsible for the production of these compounds. In this highlight, we summarize some major breakthroughs in understanding the genes and regulation of fungal natural product synthesis and introduce the current state of knowledge on the spatial and temporal control of fungal natural product synthesis.


Nat. Prod. Rep., 2014, Advance Article

DOI: 10.1039/C4NP00083H
Published 21 Aug 2014
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Genomic-scale exchange of mRNA between a parasitic plant and its hosts

Genomic-scale exchange of mRNA between a parasitic plant and its hosts | Natural Products Chemistry Breaking News | Scoop.it

Movement of RNAs between cells of a single plant is well documented, but cross-species RNA transfer is largely unexplored. Cuscuta pentagona (dodder) is a parasitic plant that forms symplastic connections with its hosts and takes up host messenger RNAs (mRNAs). We sequenced transcriptomes of Cuscuta growing on Arabidopsis and tomato hosts to characterize mRNA transfer between species and found that mRNAs move in high numbers and in a bidirectional manner. The mobile transcripts represented thousands of different genes, and nearly half the expressed transcriptome of Arabidopsis was identified in Cuscuta. These findings demonstrate that parasitic plants can exchange large proportions of their transcriptomes with hosts, providing potential mechanisms for RNA-based interactions between species and horizontal gene transfer.


Gunjune Kim, Megan L. LeBlanc, Eric K. Wafula, Claude W.  dePamphilis, James H. Westwood


Science 15 August 2014:
Vol. 345 no. 6198 pp. 808-811
DOI: 10.1126/science.1253122
NatProdChem's insight:

This will probably open a whole new field, especially for what we are interested in regarding the possible influence of these exchanges on production of metabolites from co-cultivated plants. I wonder also if the same kind of exchanges could occur with endophytes.


J.


For some recent research regarding cross-species gene transfer 

http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1004009


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Microbiota of Healthy Corals Are Active against Fungi in a Light-Dependent Manner

Microbiota of Healthy Corals Are Active against Fungi in a Light-Dependent Manner | Natural Products Chemistry Breaking News | Scoop.it
Coral reefs are intricate ecosystems that harbor diverse organisms, including 25% of all marine fish. Healthy corals exhibit a complex symbiosis between coral polyps, endosymbiotic alga, and an array of microorganisms, called the coral holobiont. Secretion of specialized metabolites by coral microbiota is thought to contribute to the defense of this sessile organism against harmful biotic and abiotic factors. While few causative agents of coral diseases have been unequivocally identified, fungi have been implicated in the massive destruction of some soft corals worldwide. Because corals are nocturnal feeders, they may be more vulnerable to fungal infection at night, and we hypothesized that the coral microbiota would have the capability to enhance their defenses against fungi in the dark. A Pseudoalteromonas sp. isolated from a healthy octocoral displayed light-dependent antifungal properties when grown adjacent to Penicillium citrinum (P. citrinum) isolated from a diseased Gorgonian octocoral. Microbial MALDI-imaging mass spectrometry (IMS) coupled with molecular network analyses revealed that Pseudoalteromonas produced higher levels of antifungal polyketide alteramides in the dark than in the light. The alteramides were inactivated by light through a photoinduced intramolecular cyclization. Further NMR studies led to a revision of the stereochemical structure of the alteramides. Alteramide A exhibited antifungal properties and elicited changes in fungal metabolite distributions of mycotoxin citrinin and citrinadins. These data support the hypothesis that coral microbiota use abiotic factors such as light to regulate the production of metabolites with specialized functions to combat opportunistic pathogens at night.

NatProdChem's insight:

Another excellent piece of work by Dorrestein's team, holistic and comprehensive approach to a complex biological phenomenon. Bravo!

PM

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Fungal natural products in research and development

Fungal natural products in research and development | Natural Products Chemistry Breaking News | Scoop.it

To date approximately 100000 fungal species are known although far more than one million are expected. The variety of species and the diversity of their habitats, some of them less exploited, allow the conclusion that fungi continue to be a rich source of new metabolites. Besides the conventional fungal isolates, an increasing interest in endophytic and in marine-derived fungi has been noticed. In addition new screening strategies based on innovative chemical, biological, and genetic approaches have led to novel fungal metabolites in recent years. The present review focuses on new fungal natural products published from 2009 to 2013 highlighting the originality of the structures and their biological potential. Furthermore synthetic products based on fungal metabolites as well as new developments in the uses or the biological activity of known compounds or new derivatives are discussed.


Anja Schueffler*a and   Timm Anke*a  
Show Affiliations
Nat. Prod. Rep., 2014, Advance Article


DOI: 10.1039/C4NP00060A


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HCNMBC – A pulse Sequence for H-(C)-N Multiple Bond Correlations at Natural Isotopic Abundance

HCNMBC – A pulse Sequence for H-(C)-N Multiple Bond Correlations at Natural Isotopic Abundance | Natural Products Chemistry Breaking News | Scoop.it


Journal of Magnetic ResonanceDOI: 10.1016/j.jmr.2014.07.011

We propose a pulse sequence, HCNMBC for multiple-bond H-(C)-N correlation experiments via one-bond1J(C,H) and one- or multiple bond nJ(N,C) coupling constants (typically n = 1 - 3) at the natural isotopic abundance. A new adiabatic refocussing sequence is introduced to provide accurate and robust refocussing of both chemical shift and J-evolution over wide ranges of C-13 and N-15 frequencies. It is demonstrated that the proposed pulse sequence provides high quality spectra even for sub-milligram samples. We show that when a 1.7 mm CryoProbe is available as little as 10 ug of glycine in D2O is sufficient to obtain the HCNMBC spectrum in ca 12 hrs. The preliminary results indicate that the pulse sequence has a great potential in the structure determination of nitrogen heterocycles especially in cases where synthesis produces regioisomers

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Renaissance of Natural Products Chemistry - Virtual Issue

Renaissance of Natural Products Chemistry - Virtual Issue | Natural Products Chemistry Breaking News | Scoop.it

Natural products are compounds made by living organisms―typically plants, microbes, and marine organisms but also insects and even mammals―that serve to propagate the species. Predating recorded history, the use of natural products for medicinal purposes has long benefited human societies. The poppy Papaver somniferum and its product opium (containing the key pharmacologically active natural product morphine) were cultivated and consumed by Neolithic tribes dating back more than 8000 years. Even today, about 40% of prescription drugs are natural products, or derive from them. "Natural products remain an important source of therapeutic drug leads and continue to inspire new approaches to problems in organic chemistry." Science has been elevated by the study of natural products. Organic chemists are innately fascinated with the intricacy of complex natural product structures, freighted with latent potential for synthetic design and expression of talent in the art of total synthesis. Pharmacologists, who measure biological properties of natural products, are often astounded by the potency and selectivity of the effects on cellular and organismal physiology. In the new millennium, there is a tendency among some to “retire” the field as a mature science, a presumption that is belied by the vigorous reprise of vitality in contemporary natural products chemistry. Here, in this ACS Virtual Issue, we can read of this steady ascendancy, augmented and propelled by new technologies in spectroscopy, synthesis, and genomics that link to allied fields in biology, computational chemistry―and yes―new classes of molecular structures. I invite you to peruse, read, and immerse your attention in 22 fine articles―highlighted and summarized from the ACS publications Organic Letters, The Journal of Organic Chemistry, and Journal of the American Chemical Society―that frame 22 stories of discovery, surprise, and scientific enlightenment.

- Tadeusz Molinski, Virtual Issue Guest Editor

NatProdChem's insight:

A must read for you NP chemists fellows!


J.

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Marine Drugs | Free Full-Text | Activation of Dormant Secondary Metabolite Production by Introducing Neomycin Resistance into the Deep-Sea Fungus, Aspergillus versicolor ZBY-3

Marine Drugs | Free Full-Text | Activation of Dormant Secondary Metabolite Production by Introducing Neomycin Resistance into the Deep-Sea Fungus, Aspergillus versicolor ZBY-3 | Natural Products Chemistry Breaking News | Scoop.it
A new ultrasound-mediated approach has been developed to introduce neomycin-resistance to activate silent pathways for secondary metabolite production in a bio-inactive, deep-sea fungus, Aspergillus versicolor ZBY-3. Upon treatment of the ZBY-3 spores with a high concentration of neomycin by proper ultrasound irradiation, a total of 30 mutants were obtained by single colony isolation. The acquired resistance of the mutants to neomycin was confirmed by a resistance test. In contrast to the ZBY-3 strain, the EtOAc extracts of 22 of the 30 mutants inhibited the human cancer K562 cells, indicating that these mutants acquired a capability to produce antitumor metabolites. HPLC-photodiode array detector (PDAD)-UV and HPLC-electron spray ionization (ESI)-MS analyses of the EtOAc extracts of seven bioactive mutants and the ZBY-3 strain indicated that diverse secondary metabolites have been newly produced in the mutant extracts in contrast to the ZBY-3 extract. The followed isolation and characterization demonstrated that six metabolites, cyclo(d-Pro-d-Phe) (1), cyclo(d-Tyr-d-Pro) (2), phenethyl 5-oxo-l-prolinate (3), cyclo(l-Ile-l-Pro) (4), cyclo(l-Leu-l-Pro) (5) and 3β,5α,9α-trihydroxy-(22E,24R)-ergosta-7,22-dien-6-one (6), were newly produced by the mutant u2n2h3-3 compared to the parent ZBY-3 strain. Compound 3 was a new compound; 2 was isolated from a natural source for the first time, and all of these compounds were also not yet found in the metabolites of other A. versicolor strains. Compounds 1–6 inhibited the K562 cells, with inhibition rates of 54.6% (1), 72.9% (2), 23.5% (3), 29.6% (4), 30.9% (5) and 51.1% (6) at 100 μg/mL, and inhibited also other human cancer HL-60, BGC-823 and HeLa cells, to some extent. The present study demonstrated the effectiveness of the ultrasound-mediated approach to activate silent metabolite production in fungi by introducing acquired resistance to aminoglycosides and its potential for discovering new compounds from silent fungal metabolic pathways. This approach could be applied to elicit the metabolic potentials of other fungal isolates to discover new compounds from cryptic secondary metabolites.


Mar. Drugs 2014, 12(8), 4326-4352; doi:10.3390/md12084326
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Detecting chirality | Chemistry World

Detecting chirality | Chemistry World | Natural Products Chemistry Breaking News | Scoop.it
Katia Moskvitch finds out about the latest techniques to determining a molecule’s chirality
NatProdChem's insight:

Most of you are already aware of these, but that's a good introduction for the others. While OR, CD are common in NPs labs, VCD and to a lower extent NMR are slowly but surely showing up.


The mass spectrometry approach is still science-fiction in the case of natural products, but who knows what will happen next…


J.

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Oxidative rearrangements during fungal biosynthesis - Natural Product Reports

Oxidative rearrangements during fungal biosynthesis - Natural Product Reports | Natural Products Chemistry Breaking News | Scoop.it

Oxidative rearrangements are key reactions during the biosyntheses of many secondary metabolites in fungi. This review highlights the most important examples of these reactions and aims to draw together key mechanistic themes to allow a better understanding and future exploitation of this key class of fungal catalysts.


Show Affiliations
Nat. Prod. Rep., 2014, Advance Article


DOI: 10.1039/C4NP00059E

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