MUSCLE : automated multi-objective evolutionary optimization of targeted LC-MS/MS analysis:Automated multi-objective evolutionary optimization of targeted LC-MS/MS analysis

Summary: Developing liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses of (bio)chemicals is both time consuming and challenging, largely because of the large number of LC and MS instrument parameters that need to be optimized. This bottleneck significantly impedes our ability to establish new (bio)analytical methods in fields such as pharmacology, metabolomics and pesticide research. We report the development of a multi-platform, user-friendly software tool MUSCLE (multi-platform unbiased optimization of spectrometry via closed-loop experimentation) for the robust and fully automated multi-objective optimization of targeted LC-MS/MS analysis. MUSCLE shortened the analysis times and increased the analytical sensitivities of targeted metabolite analysis, which was demonstrated on two different manufacturer’s LC-MS/MS instruments. Availability and implementation: Available at http://www.muscleproject.org. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online

Advances in decomposing complex metabolite mixtures using substructure- and network-based computational metabolomics approaches

Covering: up to the end of 2020 Recently introduced computational metabolome mining tools have started to positively impact the chemical and biological interpretation of untargeted metabolomics analyses. We believe that these current advances make it possible to start decomposing complex metabolite mixtures into substructure and chemical class information, thereby supporting pivotal tasks in metabolomics analysis including metabolite annotation, the comparison of metabolic profiles, and network analyses. In this review, we highlight and explain key tools and emerging strategies covering 2015 up to the end of 2020. The majority of these tools aim at processing and analyzing liquid chromatography coupled to mass spectrometry fragmentation data. We start with defining what substructures are, how they relate to molecular fingerprints, and how recognizing them helps to decompose complex mixtures. We continue with chemical classes that are based on the presence or absence of particular molecular scaffolds and/or functional groups and are thus intrinsically related to substructures. We discuss novel tools to mine substructures, annotate chemical compound classes, and create mass spectral networks from metabolomics data and demonstrate them using two case studies. We also review and speculate about the opportunities that NMR spectroscopy-based metabolome mining of complex metabolite mixtures offers to discover substructures and chemical classes. Finally, we will describe the main benefits and limitations of the current tools and strategies that rely on them, and our vision on how this exciting field can develop toward repository-scale-sized metabolomics analyses. Complementary sources of structural information from genomics analyses and well-curated taxonomic records are also discussed. Many research fields such as natural products discovery, pharmacokinetic and drug metabolism studies, and environmental metabolomics increasingly rely on untargeted metabolomics to gain biochemical and biological insights. The here described technical advances will benefit all those metabolomics disciplines by transforming spectral data into knowledge that can answer biological questions

Supporting information MS Gersemiols 2015

outputs from Gaussian NMR calculations<br

Article Absolute Configuration of the New 3-epi-cladocroic Acid from the Mediterranean Sponge Haliclona fulva

metabolite

Structure Revision of Microginins 674 and 690 from the Cultured Cyanobacterium Microcystis aeruginosa

International audienceThe structures of the commercially available microginins 674 and 690 isolated from a cultured strain of Microcystis aeruginosa and only recently characterized have been revisited. Using NMR and HRMS/MS data, an inversion of two amino acids, N-methylmethionine and tyrosine, in the structure of these metabolites is unambiguously demonstrated. These results highlight the importance of careful examination of spectroscopic data for the proposition of structures of natural products, especially when they are of commercial value

Deep metabolome annotation in natural products research: towards a virtuous cycle in metabolite identification

Natural products (NPs) research is changing and rapidly adopting cutting-edge tools, which radically transform the way to characterize extracts and small molecules. With the innovations in metabolomics, early integration of deep metabolome annotation information allows to efficiently guide the isolation of valuable NPs only and, in parallel, to generate massive metadata sets for the study of given extracts under various perspectives. This is the case for chemotaxonomy studies where common biosynthetic traits among species can be evidenced, but also for drug discovery purpose where such traits, in combination with bioactivity studies on extracts, may evidence bioactive molecules even before their isolation. One of the major bottlenecks of such studies remains the level of accuracy at which NPs can be identified. We discuss here the advancements in LC-MS and associated mining methods by addressing what would be ideal and what is achieved today. We propose future developments for reinforcing generic NPs databases both in the spectral and structural dimensions by heading towards a virtuous metabolite identification cycle allowing annotation of both known and unreported metabolites in an iterative manner. Such approaches could significantly accelerate and improve our knowledge of the huge chemodiversity found in nature

Métabolisme secondaire d'éponges marines méditerranéennes (du métabolome à l'élucidation des voies de biosynthèse)

Le groupe Substances Naturelles Marines du LCMBA (UMR 6001 CNRS-UNS) se consacre à l isolement et à la caractérisation structurale de nouvelles molécules à partir d organismes invertébrés marins spongiaires principalement). Ce manuscrit présente les travaux de recherche réalisés sur cinq éponges, Latrunculia citharistae, Dyctyonella incisa, Haliclona fulva, Pandaros acanthifolium et Axinella damicornis et un cnidaire Parazoanthus axinellae. L. citharistae est une éponge profonde de Méditerranée qui a été étudiée pour la première fois et a permis l isolement d une nouvelle molécule appartemant à la famille des batzellines : le citharoxazole. Une nouvelle saponine a été isolée de l éponge Dyctyonella incisa, et deux dérivés d acides gras ont pu être identifiés à partir de l éponge Haliclona fulva. L utilisation d une technique moderne de modélisation théorique (TDDFT) de spectre de dichroisme circulaire (ECD) a permis de déterminer la configuration absolue des différentes molécules isolées. Enfin, nous nous sommes intéressés à la biosynthèse d une molécule importante de la famille des pyrroles-2-aminoimidazoles (P-2-Ais) par incorporation in vivo de précurseurs radiomarqués. Cette étude nous a permis de confirmer l utilisation de la proline pour la biosynthèse de l oroidine. L utilisation du même protocole nous a permis de conclure sur la nature du précurseur de la deuxième partie de la molécule.Ongoing research of the Marine Natural Products group of the LCMBA (UMR 6001 CNRS-UNS) focus on the isolation and the characterization of new secondary metabollites isolated from marine invertabrates (mainly sponges). This manuscript presents our works on five marine sponges, Latrunculia citharistae, Dyctyonella incisa, Haliclona fulva, Pandaros acanthifolium and Axinella damicornis and a cnidarian Parazoanthus axinellae. L. citharistae is a deep sponge from the Mediterranean Sea which has been studied for the first time and lead to the isolation of a new compound from the batzelline family : cytharoxanole. A new saponin has been isolated from the sponge D. incise from the strait of Gilbratar and two new fatty acid derivatives have been identified form the H. fulva. The use of a recently theoretical modelisation tool (TDDFT) of electronic cicular dichroism (ECD) allowed the determination of the absolute configuration of the isolated nex compounds. Finally, we focused on the oroidin biosynthesis, an important compound of the pyrrole-2-imidazole family (P-2-AI) by in vivo incorporation of radiolabeled precursors. These studies confirm the incorporation of proline in oroidin, but also lead to the identification of the precursor of the imidazole part of the compound.NICE-BU Sciences (060882101) / SudocSudocFranceF

Rapid Identification of Antioxidant Compounds of Genista saharae Coss. &amp; Dur. by Combination of DPPH Scavenging Assay and HPTLC-MS

Genista species are sources of antioxidant phenolic compounds such as O- and C-glycosylflavonoids and isoflavonoids. A combination of a DPPH scavenging assay with HPTLC-MS, a fast and efficient method for identification of bioactive compounds, has been applied for evaluation of the radical scavenging activity of metabolites from Genista saharae Coss. &amp; Dur. Different organs collected at various periods have been compared. Identification of antioxidant compounds was obtained by elution of the major DPPH-inhibition zones. The resulting HPTLC-MS analysis under moderately polar conditions, coupled to the DPPH results led to the putative identification of two antioxidant isoflavone aglycones: 3\u27,4\u27,5,7-tetrahydroxyisoflavone (1) and ficuisoflavone (3), whereas polar migration conditions led to the identification of the glycosides 5-methoxy-4\u27,7-trihydroxy-8-glucopyranosylisoflavone (4) and 4\u27,5-dihydroxy-7-methoxyisoflavone-4\u27-O-β-D-gluco-pyranoside (5). Evaluation of percentage of inhibition of DPPH radical by the purified isoflavone 4 from the root extract showed that it affords a moderate contribution to the total radical scavenging activity of the extract

Eryloside W, a triterpenoid saponin from the sponge Dictyonella marsilii

International audienceA new saponin derivative named eryloside W was isolated from the marine sponge Dictyonella marsilii (Demospongiae, Halichondrida, Dictyonellidae). The structure of the compound was elucidated through extensive use of 1D and 2D nuclear magnetic resonance and mass spectrometry. Determination of the absolute configuration was performed using electronic circular dichroism (ECD) by comparison of experimental and time dependent density functional theory (TDDFT) calculated spectra. This is the first occurrence of a saponin derivative produced by a marine sponge present in the Mediterranean. (C) 2015 Phytochemical Society of Europe. Published by Elsevier B.V. All rights reserved