Natural Products ...
Follow
Find
89.6K views | +96 today
Natural Products Chemistry Breaking News
A recompilation of news and links about natural products, organic chemistry and science more generally ...
Curated by NatProdChem
Your new post is loading...
Your new post is loading...
Scooped by NatProdChem
Scoop.it!

How to generate journal insights using visualization techniques - Editors' Update - Your network for knowledge

How to generate journal insights using visualization techniques - Editors' Update - Your network for knowledge | Natural Products Chemistry Breaking News | Scoop.it
Editors and publishers are always curious to learn how their journal is performing compared to others in the field. They are also keen to discover whether
more...
No comment yet.
Scooped by NatProdChem
Scoop.it!

Welcome to the Fungal Natural Products themed issue! « Natural Products Blog

Welcome to the Fungal Natural Products themed issue! « Natural Products Blog | Natural Products Chemistry Breaking News | Scoop.it
NatProdChem's insight:
more...
No comment yet.
Scooped by NatProdChem
Scoop.it!

A new family of iron-dependent halogenases acts on freestanding substrates : Nature Chemical Biology

A new family of iron-dependent halogenases acts on freestanding substrates : Nature Chemical Biology | Natural Products Chemistry Breaking News | Scoop.it
Halogenases, or enzymes that perform oxidative halogenations, exist in a variety of biosynthetic pathways and modify substrates attached to carrier proteins. Biochemical evidence defines a chlorinase that breaks this rule, acting on soluble substrates.


Regio- and stereospecific incorporation of a halogen atom to an unactivated sp3 carbon in a freestanding molecule is a challenging transformation that is currently missing in the inventory of enzyme-mediated reactions. Here we report what is to our knowledge the first example of a nonheme iron enzyme (WelO5) in the welwitindolinone biosynthetic pathway that can monochlorinate an aliphatic carbon in 12-epi-fischerindole U and 12-epi-hapalindole C, substrates that are free from peptidyl or acyl carrier protein.


Nature Chemical Biology
 
(2014)
 
doi:10.1038/nchembio.1625
NatProdChem's insight:

Expanding the range of known halogenases ...

more...
No comment yet.
Scooped by NatProdChem
Scoop.it!

Exploring the Scaffold Universe of Kinase Inhibitors

Exploring the Scaffold Universe of Kinase Inhibitors | Natural Products Chemistry Breaking News | Scoop.it

The scaffold concept was applied to systematically determine, analyze, and compare core structures of kinase inhibitors. From publicly available inhibitors of the human kinome, scaffolds and cyclic skeletons were systematically extracted and organized taking activity data, structural relationships, and retrosynthetic criteria into account. Scaffold coverage varied greatly across the kinome, and many scaffolds representing compounds with different activity profiles were identified. The majority of kinase inhibitor scaffolds were involved in well-defined yet distinct structural relationships, which had different consequences on compound activity. Scaffolds exclusively representing highly potent compounds were identified as well as structurally analogous scaffolds with very different degrees of promiscuity. Scaffold relationships presented herein suggest a variety of hypotheses for inhibitor design. Our detailed organization of the kinase inhibitor scaffold universe with respect to different activity and structural criteria, all scaffolds, and the original compound data assembled for our analysis are made freely available.


J. Med. Chem., Article ASAP
DOI: 10.1021/jm501237k
more...
No comment yet.
Scooped by NatProdChem
Scoop.it!

MDN-0104, an Antiplasmodial Betaine Lipid from Heterospora chenopodii

MDN-0104, an Antiplasmodial Betaine Lipid from Heterospora chenopodii | Natural Products Chemistry Breaking News | Scoop.it

Bioassay-guided fractionation of the crude fermentation extract of Heterospora chenopodii led to the isolation of a novel monoacylglyceryltrimethylhomoserine (1). The structure of this new betaine lipid was elucidated by detailed spectroscopic analysis using one- and two-dimensional NMR experiments and high-resolution mass spectrometry. Compound 1 displayed moderate in vitro antimalarial activity against Plasmodium falciparum, with an IC50 value of 7 μM. This betaine lipid is the first monoacylglyceryltrimethylhomoserine ever reported in the Fungi, and its acyl moiety also represents a novel natural 3-keto fatty acid. The new compound was isolated during a drug discovery program aimed at the identification of new antimalarial leads from a natural product library of microbial extracts. Interestingly, the related fungus Heterospora dimorphospora was also found to produce compound 1, suggesting that species of this genus may be a promising source of monoacylglyceryltrimethylhomoserines.


J. Nat. Prod., Article ASAP
DOI: 10.1021/np500577v
Publication Date (Web): September 12, 2014
more...
No comment yet.
Scooped by NatProdChem
Scoop.it!

Sterhirsutins A and B, Two New Heterodimeric Sesquiterpenes with a New Skeleton from the Culture of Stereum hirsutum Collected in Tibet Plateau

Sterhirsutins A and B, Two New Heterodimeric Sesquiterpenes with a New Skeleton from the Culture of Stereum hirsutum Collected in Tibet Plateau | Natural Products Chemistry Breaking News | Scoop.it

Two new heterodimeric sesquiterpenes, sterhirsutins A (1) and B (2), and two new sesquiterpenes, hirsutic acids D–E (3 and 4), were identified from the culture of Stereum hirsutum. The absolute configurations in 1 and 2 were confirmed by single-crystal X-ray diffraction experiments and electronic circular dichroism (ECD) calculations. Compounds 1 and2 are likely biosynthesized from a hirsutane-type sesquiterpene and α-humulene by a hetero-Diels–Alder cycloaddition. Compounds 14 showed cytotoxicity against K562 and HCT116 cell lines.


Qiu-Yue Qi Li Bao Jin-Wei Ren Jun-Jie Han ,Zong-Yao Zhang §Yi Li Yi-Jian Yao Rui Cao §, and Hong-Wei Liu
Org. Lett., Article ASAP
DOI: 10.1021/ol502441n


more...
No comment yet.
Scooped by NatProdChem
Scoop.it!

Elucidation of the Cryptic Epimerase Activity of Redox-Inactive Ketoreductase Domains from Modular Polyketide Synthases by Tandem Equilibrium Isotope Exchange

Elucidation of the Cryptic Epimerase Activity of Redox-Inactive Ketoreductase Domains from Modular Polyketide Synthases by Tandem Equilibrium Isotope Exchange | Natural Products Chemistry Breaking News | Scoop.it

Many modular polyketide synthases harbor one or more redox-inactive domains of unknown function that are highly homologous to ketoreductase (KR) domains. A newly developed tandem equilibrium isotope exchange (EIX) assay has now established that such “KR0” domains catalyze the biosynthetically essential epimerization of transient (2R)-2-methyl-3-ketoacyl-ACP intermediates to the corresponding (2S)-2-methyl-3-ketoacyl-ACP diastereomers. Incubation of [2-2H]-(2R,3S)-2-methyl-3-hydroxypentanoyl-SACP ([2-2H]-3b) with the EryKR30 domain from module 3 of the 6-deoxyerythronolide B synthase, and the redox-active, nonepimerizing EryKR6 domain and NADP+ resulted in time- and cofactor-dependent washout of deuterium from 3b, as a result of EryKR30-catalyzed epimerization of transiently generated [2-2H]-2-methyl-3-ketopentanoyl-ACP (4). Similar results were obtained with redox-inactive PicKR30 from module 3 of the picromycin synthase. Four redox-inactive mutants of epimerase-active EryKR1 were engineered by mutagenesis of the NADPH binding site of this enzyme. Tandem EIX established that these EryKR10 mutants retained the intrinsic epimerase activity of the parent EryKR1 domain. These results establish the intrinsic epimerase activity of redox-inactive KR0 domains, rule out any role for the NADPH cofactor in epimerization, and provide a general experimental basis for decoupling the epimerase and reductase activities of a large class of PKS domains.


J. Am. Chem. Soc., 2014136 (29), pp 10190–10193
DOI: 10.1021/ja5056998
Publication Date (Web): July 8, 2014




more...
No comment yet.
Scooped by NatProdChem
Scoop.it!

Tramadol—A True Natural Product? - Kusari - 2014 - Angewandte Chemie International Edition - Wiley Online Library

Tramadol—A True Natural Product? - Kusari - 2014 - Angewandte Chemie International Edition - Wiley Online Library | Natural Products Chemistry Breaking News | Scoop.it

We have independently investigated the source of tramadol, a synthetic analgesic largely used for treating moderate to severe pain in humans, recently found in the roots of the Cameroonian medicinal plant, Nauclea latifolia. We found tramadol and its three major mammalian metabolites (O-desmethyltramadol, N-desmethyltramadol, and 4-hydroxycyclohexyltramadol) in the roots of N. latifolia and five other plant species, and also in soil and local water bodies only in the Far North region of Cameroon. The off-label administration of tramadol to cattle in this region leads to cross-contamination of the soil and water through feces and urine containing parent tramadol as well as tramadol metabolites produced in the animals. These compounds can then be absorbed by the plant roots and also leached into the local water supplies. The presence of tramadol in roots is, thus, due to an anthropogenic contamination with the synthetic compound.


Angewandte Chemie International Edition
  1. Dr. Souvik Kusari1,
  2. Dr. Simplice Joel N. Tatsimo2,
  3. Dr. Sebastian Zühlke1,
  4. Dr. Ferdinand M. Talontsi1,
  5. Prof. Dr. Simeon Fogue Kouam3 and
  6. Prof. Dr. Michael Spiteller1,*

Article first published online: 12 SEP 2014

DOI: 10.1002/anie.201406639

NatProdChem's insight:

Tramadol was found lately to be present in the roots of Nauclea latifolia, a medicinal plant from Cameroon and believed to be an original secondary metabolite from the plant, thus beiing an interesting case of synthetic drug <> natural product analogy without previous knowledge of the natural products structure. See initial paper here http://onlinelibrary.wiley.com/doi/10.1002/ange.201305697/abstract

The story might be a little bit different ...

more...
No comment yet.
Scooped by NatProdChem
Scoop.it!

Assembly-line synthesis of organic molecules with tailored shapes : Nature

Assembly-line synthesis of organic molecules with tailored shapes : Nature | Natural Products Chemistry Breaking News | Scoop.it

Molecular ‘assembly lines’, in which organic molecules undergo iterative processes such as chain elongation and functional group manipulation, are found in many natural systems, including polyketide biosynthesis. Here we report the creation of such an assembly line using the iterative, reagent-controlled homologation of a boronic ester. This process relies on the reactivity of α-lithioethyl tri-isopropylbenzoate, which inserts into carbon–boron bonds with exceptionally high fidelity and stereocontrol; each chain-extension step generates a new boronic ester, which is immediately ready for further homologation. We used this method to generate organic molecules that contain ten contiguous, stereochemically defined methyl groups. Several stereoisomers were synthesized and shown to adopt different shapes—helical or linear—depending on the stereochemistry of the methyl groups. This work should facilitate the rational design of molecules with predictable shapes, which could have an impact in areas of molecular sciences in which bespoke molecules are required.


Nature 513183–188 (11 September 2014) doi:10.1038/nature13711
more...
No comment yet.
Scooped by NatProdChem
Scoop.it!

Natural product and natural product derived drugs in clinical trials - Natural Product Reports (RSC Publishing)

Natural product and natural product derived drugs in clinical trials - Natural Product Reports (RSC Publishing) | Natural Products Chemistry Breaking News | Scoop.it

Covering: 2008–2013. Previous review: (2008, issue 25, p. 475)


« There are a significant number of natural product (NP) drugs in development. We review the 100 NP and NP-derived compounds and 33 Antibody Drug Conjugates (ADCs) with a NP-derived cytotoxic component being evaluated in clinical trials or in registration at the end of 2013. 38 of these compounds and 33 ADCs are being investigated as potential oncology treatments, 26 as anti-infectives, 19 for the treatment of cardiovascular and metabolic diseases, 11 for inflammatory and related diseases and 6 for neurology. There was a spread of the NP and NP-derived compounds through the different development phases (17 in phase I, 52 in phase II, 23 in phase III and 8 NDA and/or MAA filed), while there were 23 ADCs in phase I and 10 in phase II. 50 of these 100 compounds were either NPs or semi-synthetic (SS) NPs, which indicated the original NP still plays an important role. NP and NP-derived compounds for which clinical trials have been halted or discontinued since 2008 are listed in the Supplementary Information. The 25 NP and NP-derived drugs launched since 2008 are also reviewed, and late stage development candidates and new NP drug pharmacophores analysed. The short term prospect for new NP and NP-derived drug approvals is bright, with 31 compounds in phase III or in registration, which should ensure a steady stream of approvals for at least the next five years. However, there could be future issues for new drug types as only five new drug pharmacophores discovered in the last 15 years are currently being evaluated in clinical trials. The next few years will be critical for NP-driven lead discovery, and a concerted effort is required to identify new biologically active pharmacophores and to progress these and existing compounds through pre-clinical drug development into clinical trials. »




Nat. Prod. Rep., 2014, Advance Article
DOI: 10.1039/C4NP00064A
Received 19 May 2014, First published online 10 Sep 2014
NatProdChem's insight:

An interesting review… Many "new R-group, new compound" cases these last years…


Epigallocatechin gallate is the new Panacea: Alzheimer’s disease
(phase II/III, NCT00951834), Duchenne Muscular Dystrophy
(phase II, NCT01183767) and Huntington’s Disease (phase II,
NCT01357681),  Cardiac Amyloid Light-chain (phase II, NCT02015312).
Many cyclopeptides, some Voodoo medicine (tetrodotoxin), coming back of stilbenoids (but from bacterias) with the anti-inflammatory WBI-1001 and a follow-up on combretastatin and derivatives. The locked version of fosbretastation, BNC105P, is a nice one, and is actually tested for topical psoriasis treatment in phase II.


As usual with this kind of reviews it is hard to manage such an amount of information, but that's a good reference on what are the current trends. Which I actually define as: Antibodies, cyclopeptides, and polyphenols derivatives… But you


J.

more...
No comment yet.
Scooped by NatProdChem
Scoop.it!

Oxazinin A, a Pseudodimeric Natural Product of Mixed Biosynthetic Origin from a Filamentous Fungus

Oxazinin A, a Pseudodimeric Natural Product of Mixed Biosynthetic Origin from a Filamentous Fungus | Natural Products Chemistry Breaking News | Scoop.it

A racemic, prenylated polyketide dimer, oxazinin A (1), was isolated from a novel filamentous fungus in the class Eurotiomycetes, and its structure was elucidated spectroscopically. The pentacyclic structure of oxazinin A (1) is a unique combination of benzoxazine, isoquinoline, and a pyran ring. Oxazinin A (1) exhibited antimycobacterial activity and modestly antagonized transient receptor potential (TRP) channels.


†Department of Medicinal Chemistry and ‡Department of Pharmacology and Toxicology, L. S. Skaggs Pharmacy Institute, University of Utah, Salt Lake City, Utah 84112 United States
Org. Lett., Article ASAP
DOI: 10.1021/ol502227x


more...
No comment yet.
Scooped by NatProdChem
Scoop.it!

The first non-indolyl cruciferous phytoalexins: Nasturlexins and tridentatols, a striking convergent evolution of defenses in terrestrial plants and marine animals?

The first non-indolyl cruciferous phytoalexins: Nasturlexins and tridentatols, a striking convergent evolution of defenses in terrestrial plants and marine animals? | Natural Products Chemistry Breaking News | Scoop.it

Elicited metabolites from the crucifer Nasturtium officinale are investigated.

The first isolation of cruciferous phytoalexins not derived from tryptophan is reported.

Previously one of these phytoalexins was only found in a marine animal (Tridentata marginata).

The antifungal activity of the phytoalexins nasturlexins A and B and tridentatol C against pathogens of crucifers is evaluated.


 

Available online 21 August 2014

DOI: 10.1016/j.phytochem.2014.07.024
more...
Scooped by NatProdChem
Scoop.it!

Biosynthesis of the ergot alkaloids

Biosynthesis of the ergot alkaloids | Natural Products Chemistry Breaking News | Scoop.it

The ergots are a structurally diverse group of alkaloids derived from tryptophan 7 and dimethylallyl pyrophosphate (DMAPP) 8. The potent bioactivity of ergot alkaloids have resulted in their use in many applications throughout human history. In this highlight, we recap some of the history of the ergot alkaloids, along with a brief description of the classifications of the different ergot structures and producing organisms. Finally we describe what the advancements that have been made in understanding the biosynthetic pathways, both at the genomic and the biochemical levels. We note that several excellent review on the ergot alkaloids, including one by Wallwey and Li in Nat. Prod. Rep., have been published recently. We provide a brief overview of the ergot alkaloids, and highlight the advances in biosynthetic pathway elucidation that have been made since 2011 in Section 4.


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


DOI: 10.1039/C4NP00062E

more...
No comment yet.
Scooped by NatProdChem
Scoop.it!

A microbial biomanufacturing platform for natural and semisynthetic opioids

A microbial biomanufacturing platform for natural and semisynthetic opioids | Natural Products Chemistry Breaking News | Scoop.it
Metabolic engineering of yeast to incorporate plant and bacterial enzymes that construct and decorate morphine, along with spatial engineering to enable a spontaneous chemical reaction, provides strains capable of producing up to 130 mg/l of opioids.


10837–844 (2014)
  

doi:10.1038/nchembio.1613

more...
No comment yet.
Scooped by NatProdChem
Scoop.it!

isoMETLIN: A Database for Isotope-Based Metabolomics

isoMETLIN: A Database for Isotope-Based Metabolomics | Natural Products Chemistry Breaking News | Scoop.it

The METLIN metabolite database has become one of the most widely used resources in metabolomics for making metabolite identifications. However, METLIN is not designed to identify metabolites that have been isotopically labeled. As a result, unbiasedly tracking the transformation of labeled metabolites with isotope-based metabolomics is a challenge. Here, we introduce a new database, called isoMETLIN (http://isometlin.scripps.edu/), that has been developed specifically to identify metabolites incorporating isotopic labels. isoMETLIN enables users to search all computed isotopologues derived from METLIN on the basis of mass-to-charge values and specified isotopes of interest, such as 13C or 15N. Additionally, isoMETLIN contains experimental MS/MS data on hundreds of isotopomers. These data assist in localizing the position of isotopic labels within a metabolite. From these experimental MS/MS isotopomer spectra, precursor atoms can be mapped to fragments. The MS/MS spectra of additional isotopomers can then be computationally generated and included within isoMETLIN. Given that isobaric isotopomers cannot be separated chromatographically or by mass but are likely to occur simultaneously in a biological system, we have also implemented a spectral-mixing function in isoMETLIN. This functionality allows users to combine MS/MS spectra from various isotopomers in different ratios to obtain a theoretical MS/MS spectrum that matches the MS/MS spectrum from a biological sample. Thus, by searching MS and MS/MS experimental data, isoMETLIN facilitates the identification of isotopologues as well as isotopomers from biological samples and provides a platform to drive the next generation of isotope-based metabolomic studies.


Anal. Chem., Article ASAP
DOI: 10.1021/ac5029177
Publication Date (Web): August 28, 2014
more...
No comment yet.
Scooped by NatProdChem
Scoop.it!

The Curious Wavefunction: Happy Birthday to the man who found life slipping away from his fingers

The Curious Wavefunction: Happy Birthday to the man who found life slipping away from his fingers | Natural Products Chemistry Breaking News | Scoop.it
NatProdChem's insight:

In my quest for the secret of life I started my research in histology. Unsatisfied by the information that cellular morphology could give me about life, I turned to physiology. Finding physiology too complex, I took up pharmacology. Still finding the situation too complicated, I turned to bacteriology. But bacteria were even too complex, so I descended to the molecular level, studying chemistry and physical chemistry. After twenty years' work, I was led to conclude that to understand life we have to descend to the electronic level and to the world of wave mechanics. But electrons are just electrons and have no life at all. Evidently on the way I lost life; it had run out between my fingers.


more...
No comment yet.
Scooped by NatProdChem
Scoop.it!

A Unified Bioinspired “Aplysinopsin Cascade”: Total Synthesis of (±)-Tubastrindole B and Related Biosynthetic Congeners - Organic Letters

A Unified Bioinspired “Aplysinopsin Cascade”: Total Synthesis of (±)-Tubastrindole B and Related Biosynthetic Congeners - Organic Letters | Natural Products Chemistry Breaking News | Scoop.it

Applying a biomimetic approach, the first total synthesis of (±)-tubastrindole B is reported herein. This work features a ring-expansion cascade of a dictazole-type precursor into cycloaplysinopsin-type congeners. Moreover, the isolation of a transient biogenetic intermediate represents a milestone in the biosynthetic understanding of this family of marine alkaloids.

 Laboratoire de pharmacognosie, Université Paris-Sud, UMR CNRS 8076 BioCIS, LabEx LERMIT, Faculté de Pharmacie, 5, rue Jean-Baptiste Clément, 92296 Châtenay-Malabry, France
 Équipe “Molécules fluorées et chimie médicinale”,Université Paris-Sud, UMR CNRS 8076 BioCIS, LabEx LERMIT, Faculté de Pharmacie, 5, rue Jean-Baptiste Clément, 92296 Châtenay-Malabry, France
Org. Lett., Article ASAP
DOI: 10.1021/ol502177m


more...
No comment yet.
Scooped by NatProdChem
Scoop.it!

Conscious Brain-to-Brain Communication in Humans Using Non-Invasive Technologies

Conscious Brain-to-Brain Communication in Humans Using Non-Invasive Technologies | Natural Products Chemistry Breaking News | Scoop.it

Here we show how to link two human minds directly by integrating two neurotechnologies – BCI and CBI –, fulfilling three important conditions, namely a) being non-invasive, b) cortically based, and c) consciously driven. In this framework we provide the first demonstration of non-invasive direct communication between human minds.



  • Carles Grau, Romuald Ginhoux, Alejandro Riera,Thanh Lam Nguyen, Hubert Chauvat, Michel Berg, Julià L. Amengual, Alvaro Pascual-Leone, Giulio Ruffini
  • PlosOne
  • Published: August 19, 2014
  • DOI: 10.1371/journal.pone.0105225



more...
Herb Neu's curator insight, September 14, 6:36 AM

This is a remarkable study. It scientifically proves what has always tended to be anecdotal: Telepathy.

Scooped by NatProdChem
Scoop.it!

A Unified Strategy for the Synthesis of 7-Membered-Ring-Containing Lycopodium Alkaloids

A Unified Strategy for the Synthesis of 7-Membered-Ring-Containing Lycopodium Alkaloids | Natural Products Chemistry Breaking News | Scoop.it

A unique subset of the Lycopodium alkaloid natural products share a 7-membered-ring substructure and may potentially arise from a common biosynthetic precursor. To both explore and exploit these structural relationships, we sought to develop a unified biosynthetically inspired strategy to efficiently access these complex polycyclic alkaloids through the use of a cascade sequence. In pursuit of these goals, the first total synthesis of (+)-fastigiatine (2) was accomplished via a series of cascade reactions; we describe herein a full account of our efforts. Insight from these endeavors led to critical modifications of our synthetic strategy, which enabled the first total syntheses of (−)-himeradine A (1), (−)-lycopecurine (3), and (−)-dehydrolycopecurine (4), as well as the syntheses of (+)-lyconadin A (5) and (−)-lyconadin B (6). Our approach features a diastereoselective one-pot sequence for constructing the common 7-membered-ring core system, followed by either a biomimetic transannular Mannich reaction to access himeradine A (1), lycopecurine (3), and dehydrolycopecurine (4) or an imine reduction for lyconadins A (5) and B (6). This strategy may potentially enable access to all 7-membered-ring-containing Lycopodium alkaloids and provides additional insight into their biosynthetic origin.


Department of Chemistry and Chemical Biology,Harvard University, Cambridge, Massachusetts 02138,United States
J. Am. Chem. Soc., Article ASAP
DOI: 10.1021/ja507740u



more...
No comment yet.
Scooped by NatProdChem
Scoop.it!

New anti-infective cycloheptadepsipeptide congeners and absolute stereochemistry from the deep sea-derived Streptomyces drozdowiczii SCSIO 10141

New anti-infective cycloheptadepsipeptide congeners and absolute stereochemistry from the deep sea-derived Streptomyces drozdowiczii SCSIO 10141 | Natural Products Chemistry Breaking News | Scoop.it

Six cycloheptadepsipeptides, marformycins A–F (16), featuring a unique N-terminally formylated side chain and five non-proteinogenic amino acid residues, were isolated from the deep Sea-derivedStreptomyces drozdowiczii SCSIO 10141. The previously unsolved absolute stereochemistry of 3 and 4was determined and the structures of other four new congeners were elucidated by extensive spectroscopic, chiral-phase HPLC, and single-crystal X-ray diffraction analyses. Compounds 15 bear no cytotoxicity against a number of human tumor cell lines but show selective anti-infective activity againstMicrococcus luteus.


 

Volume 70, Issue 42, 21 October 2014, Pages 7795–7801

DOI: 10.1016/j.tet.2014.02.007




more...
No comment yet.
Scooped by NatProdChem
Scoop.it!

MIDAS: A Database-Searching Algorithm for Metabolite Identification in Metabolomics

MIDAS: A Database-Searching Algorithm for Metabolite Identification in Metabolomics | Natural Products Chemistry Breaking News | Scoop.it

A database searching approach can be used for metabolite identification in metabolomics by matching measured tandem mass spectra (MS/MS) against the predicted fragments of metabolites in a database. Here, we present the open-source MIDAS algorithm (Metabolite Identification via Database Searching). To evaluate a metabolite-spectrum match (MSM), MIDAS first enumerates possible fragments from a metabolite by systematic bond dissociation, then calculates the plausibility of the fragments based on their fragmentation pathways, and finally scores the MSM to assess how well the experimental MS/MS spectrum from collision-induced dissociation (CID) is explained by the metabolite’s predicted CID MS/MS spectrum. MIDAS was designed to search high-resolution tandem mass spectra acquired on time-of-flight or Orbitrap mass spectrometer against a metabolite database in an automated and high-throughput manner. The accuracy of metabolite identification by MIDAS was benchmarked using four sets of standard tandem mass spectra from MassBank. On average, for 77% of original spectra and 84% of composite spectra, MIDAS correctly ranked the true compounds as the first MSMs out of all MetaCyc metabolites as decoys. MIDAS correctly identified 46% more original spectra and 59% more composite spectra at the first MSMs than an existing database-searching algorithm, MetFrag. MIDAS was showcased by searching a published real-world measurement of a metabolome from Synechococcus sp. PCC 7002 against the MetaCyc metabolite database. MIDAS identified many metabolites missed in the previous study. MIDAS identifications should be considered only as candidate metabolites, which need to be confirmed using standard compounds. To facilitate manual validation, MIDAS provides annotated spectra for MSMs and labels observed mass spectral peaks with predicted fragments. The database searching and manual validation can be performed online at http://midas.omicsbio.org.


Anal. Chem., Article ASAP
DOI: 10.1021/ac5014783
Publication Date (Web): August 26, 2014


more...
No comment yet.
Scooped by NatProdChem
Scoop.it!

Pep2Path: Automated Mass Spectrometry-Guided Genome Mining of Peptidic Natural Products

Pep2Path: Automated Mass Spectrometry-Guided Genome Mining of Peptidic Natural Products | Natural Products Chemistry Breaking News | Scoop.it

Nonribosomally and ribosomally synthesized bioactive peptides constitute a source of molecules of great biomedical importance, including antibiotics such as penicillin, immunosuppressants such as cyclosporine, and cytostatics such as bleomycin. Recently, an innovative mass-spectrometry-based strategy, peptidogenomics, has been pioneered to effectively mine microbial strains for novel peptidic metabolites. Even though mass-spectrometric peptide detection can be performed quite fast, true high-throughput natural product discovery approaches have still been limited by the inability to rapidly match the identified tandem mass spectra to the gene clusters responsible for the biosynthesis of the corresponding compounds. With Pep2Path, we introduce a software package to fully automate the peptidogenomics approach through the rapid Bayesian probabilistic matching of mass spectra to their corresponding biosynthetic gene clusters. Detailed benchmarking of the method shows that the approach is powerful enough to correctly identify gene clusters even in data sets that consist of hundreds of genomes, which also makes it possible to match compounds from unsequenced organisms to closely related biosynthetic gene clusters in other genomes. Applying Pep2Path to a data set of compounds without known biosynthesis routes, we were able to identify candidate gene clusters for the biosynthesis of five important compounds. Notably, one of these clusters was detected in a genome from a different subphylum of Proteobacteria than that in which the molecule had first been identified. All in all, our approach paves the way towards high-throughput discovery of novel peptidic natural products. Pep2Path is freely available from http://pep2path.sourceforge.net/, implemented in Python, licensed under the GNU General Public License v3 and supported on MS Windows, Linux and Mac OS X.


PLOS Computational Biology is an open-access


  • Marnix H. Medema, Yared Paalvast
  • Don D. Nguyen,Alexey Melnik,
  • Pieter C. Dorrestein
  • Eriko Takano, Rainer Breitling
  • Published: September 04, 2014
more...
No comment yet.
Scooped by NatProdChem
Scoop.it!

The Most Unconscionable Drug Price Hike I Have Yet Seen. In the Pipeline:

The Most Unconscionable Drug Price Hike I Have Yet Seen. In the Pipeline: | Natural Products Chemistry Breaking News | Scoop.it
more...
No comment yet.
Scooped by NatProdChem
Scoop.it!

New Nature section : The digital toolbox

New Nature section : The digital toolbox | Natural Products Chemistry Breaking News | Scoop.it
A new section of Nature examines the software and websites that make research easier.
NatProdChem's insight:

It's all here : http://www.nature.com/news/toolbox

more...
No comment yet.
Rescooped by NatProdChem from Scientific social network
Scoop.it!

Is ResearchGate Facebook for science?

Is ResearchGate Facebook for science? | Natural Products Chemistry Breaking News | Scoop.it
Science Careers, a part of the journal Science and the American Association for the Advancement of Science, is the leading resource for job listings and career advice in the science, technology, engineering and mathematics fields. Science Careers

Via MyScienceWork
more...
Renato P. dos Santos's curator insight, September 12, 4:08 AM

I'm quite happy with it. My papers started received more attention after I joined it.