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1.
Org Lett ; 22(7): 2634-2638, 2020 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-32193935

RESUMO

Growth from spores activated a biosynthetic gene cluster in Actinomadura sp. RB29, resulting in the identification of two novel groups of halogenated polyketide natural products, named maduralactomycins and actinospirols. The unique tetracyclic and spirocyclic structures were assigned based on a combination of NMR analysis, chemoinformatic calculations, X-ray crystallography, and 13C labeling studies. On the basis of HRMS2 data, genome mining, and gene expression studies, we propose an underlying noncanonical angucycline biosynthesis and extensive post-polyketide synthase (PKS) oxidative modifications.

2.
J Cheminform ; 11(1): 55, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399811

RESUMO

Natural products (NPs), often also referred to as secondary metabolites, are small molecules synthesised by living organisms. Natural products are of interest due to their bioactivity and in this context as starting points for the development of drugs and other bioactive synthetic products. In order to select compounds from virtual libraries, Ertl et al. developed a natural product likeness score which was later published as an open data, open source implementation. Here we present NaPLeS, an easily portable, containerised, open source web application based on open data to compute natural product likeness scores for chemical libraries.

3.
Nat Chem Biol ; 15(8): 813-821, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31308532

RESUMO

Bacterial trans-acyltransferase polyketide synthases (trans-AT PKSs) are among the most complex known enzymes from secondary metabolism and are responsible for the biosynthesis of highly diverse bioactive polyketides. However, most of these metabolites remain uncharacterized, since trans-AT PKSs frequently occur in poorly studied microbes and feature a remarkable array of non-canonical biosynthetic components with poorly understood functions. As a consequence, genome-guided natural product identification has been challenging. To enable de novo structural predictions for trans-AT PKS-derived polyketides, we developed the trans-AT PKS polyketide predictor (TransATor). TransATor is a versatile bio- and chemoinformatics web application that suggests informative chemical structures for even highly aberrant trans-AT PKS biosynthetic gene clusters, thus permitting hypothesis-based, targeted biotechnological discovery and biosynthetic studies. We demonstrate the applicative scope in several examples, including the characterization of new variants of bioactive natural products as well as structurally new polyketides from unusual bacterial sources.


Assuntos
Bactérias/enzimologia , Policetídeo Sintases/metabolismo , Policetídeos/metabolismo , Sequência de Aminoácidos , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Produtos Biológicos , Modelos Químicos , Filogenia , Policetídeo Sintases/genética , Policetídeos/química , Poríferos/microbiologia , Domínios Proteicos , Especificidade por Substrato
4.
Angew Chem Int Ed Engl ; 58(32): 10766-10768, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31313429

RESUMO

"The formation of a National Research Data Infrastructure for Chemistry (NFDI4Chem), integrated into a National Research Data Infrastructure for all scientific disciplines, is a great opportunity for our discipline. Proper research data management is the basis for good scientific practice and opens up new fields of research …" Read more in the Guest Editorial by S. Herres-Pawlis et al.

5.
J Cheminform ; 11(1): 37, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31165338

RESUMO

The Ertl algorithm for automated functional groups (FG) detection and extraction of organic molecules is implemented on the basis of the Chemistry Development Kit (CDK). A distinct impact of the chosen CDK aromaticity model is demonstrated by an FG analysis of the ChEMBL database compounds. The average performance of less than a millisecond for a single-molecule FG extraction allows for fast processing of even large compound databases.

6.
Bioinformatics ; 35(19): 3752-3760, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30851093

RESUMO

MOTIVATION: Developing a robust and performant data analysis workflow that integrates all necessary components whilst still being able to scale over multiple compute nodes is a challenging task. We introduce a generic method based on the microservice architecture, where software tools are encapsulated as Docker containers that can be connected into scientific workflows and executed using the Kubernetes container orchestrator. RESULTS: We developed a Virtual Research Environment (VRE) which facilitates rapid integration of new tools and developing scalable and interoperable workflows for performing metabolomics data analysis. The environment can be launched on-demand on cloud resources and desktop computers. IT-expertise requirements on the user side are kept to a minimum, and workflows can be re-used effortlessly by any novice user. We validate our method in the field of metabolomics on two mass spectrometry, one nuclear magnetic resonance spectroscopy and one fluxomics study. We showed that the method scales dynamically with increasing availability of computational resources. We demonstrated that the method facilitates interoperability using integration of the major software suites resulting in a turn-key workflow encompassing all steps for mass-spectrometry-based metabolomics including preprocessing, statistics and identification. Microservices is a generic methodology that can serve any scientific discipline and opens up for new types of large-scale integrative science. AVAILABILITY AND IMPLEMENTATION: The PhenoMeNal consortium maintains a web portal (https://portal.phenomenal-h2020.eu) providing a GUI for launching the Virtual Research Environment. The GitHub repository https://github.com/phnmnl/ hosts the source code of all projects. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

7.
Chemistry ; 24(44): 11319-11324, 2018 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-29846024

RESUMO

We characterized two key biosynthetic intermediates of the intriguing rubterolone family (tropolone alkaloids) that contain a highly reactive pyran moiety (in equilibrium with the hydrolyzed 1,5-dione form) and undergo spontaneous pyridine formation in the presence of primary amines. We exploited the intrinsic reactivity of the pyran moiety and isolated several new rubterolone derivatives, two of which contain a unique thiazolidine moiety. Three rubterolone derivatives were chemically modified with fluorescence and biotin tags using peptide coupling and click reaction. Overall, eight derivatives were fully characterized by HRMS/MS and 1D and 2D NMR spectroscopy and their antimicrobial, cytotoxic, anti-inflammatory and antiparasitic activities evaluated.

8.
Int J Mol Sci ; 19(5)2018 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-29734799

RESUMO

The relatively new research discipline of Eco-Metabolomics is the application of metabolomics techniques to ecology with the aim to characterise biochemical interactions of organisms across different spatial and temporal scales. Metabolomics is an untargeted biochemical approach to measure many thousands of metabolites in different species, including plants and animals. Changes in metabolite concentrations can provide mechanistic evidence for biochemical processes that are relevant at ecological scales. These include physiological, phenotypic and morphological responses of plants and communities to environmental changes and also interactions with other organisms. Traditionally, research in biochemistry and ecology comes from two different directions and is performed at distinct spatiotemporal scales. Biochemical studies most often focus on intrinsic processes in individuals at physiological and cellular scales. Generally, they take a bottom-up approach scaling up cellular processes from spatiotemporally fine to coarser scales. Ecological studies usually focus on extrinsic processes acting upon organisms at population and community scales and typically study top-down and bottom-up processes in combination. Eco-Metabolomics is a transdisciplinary research discipline that links biochemistry and ecology and connects the distinct spatiotemporal scales. In this review, we focus on approaches to study chemical and biochemical interactions of plants at various ecological levels, mainly plant⁻organismal interactions, and discuss related examples from other domains. We present recent developments and highlight advancements in Eco-Metabolomics over the last decade from various angles. We further address the five key challenges: (1) complex experimental designs and large variation of metabolite profiles; (2) feature extraction; (3) metabolite identification; (4) statistical analyses; and (5) bioinformatics software tools and workflows. The presented solutions to these challenges will advance connecting the distinct spatiotemporal scales and bridging biochemistry and ecology.


Assuntos
Ecologia , Metabolômica/tendências , Plantas/genética , Plantas/metabolismo
9.
Magn Reson Chem ; 56(8): 703-715, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29656574

RESUMO

Even though NMR has found countless applications in the field of small molecule characterization, there is no standard file format available for the NMR data relevant to structure characterization of small molecules. A new format is therefore introduced to associate the NMR parameters extracted from 1D and 2D spectra of organic compounds to the proposed chemical structure. These NMR parameters, which we shall call NMReDATA (for nuclear magnetic resonance extracted data), include chemical shift values, signal integrals, intensities, multiplicities, scalar coupling constants, lists of 2D correlations, relaxation times, and diffusion rates. The file format is an extension of the existing Structure Data Format, which is compatible with the commonly used MOL format. The association of an NMReDATA file with the raw and spectral data from which it originates constitutes an NMR record. This format is easily readable by humans and computers and provides a simple and efficient way for disseminating results of structural chemistry investigations, allowing automatic verification of published results, and for assisting the constitution of highly needed open-source structural databases.


Assuntos
Armazenamento e Recuperação da Informação/normas , Espectroscopia de Ressonância Magnética/estatística & dados numéricos , Compostos Orgânicos/química , Bases de Dados de Compostos Químicos/estatística & dados numéricos , Software/normas
10.
Org Biomol Chem ; 16(19): 3553-3555, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29532847

RESUMO

A new bilirubin oxidation end product (BOX) was isolated and characterized. The formation of the so-called Z-BOX C proceeds from bilirubin via propentdyopents as intermediates. This BOX was detected in pathological human bile samples using liquid chromatography/mass spectrometry and has potential relevance for liver dysfunction and cerebral vasospasms.


Assuntos
Bilirrubina/química , Bilirrubina/metabolismo , Bile/metabolismo , Humanos , Oxirredução
11.
Metabolomics ; 14(1): 16, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29479297

RESUMO

Introduction: Data sharing is being increasingly required by journals and has been heralded as a solution to the 'replication crisis'. Objectives: (i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals' policies to those that publish the most metabolomics papers. Methods: A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications. Results: Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data. Conclusion: Further efforts are required to improve data sharing in metabolomics.

12.
Anal Chem ; 90(1): 649-656, 2018 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-29035042

RESUMO

NMR is a widely used analytical technique with a growing number of repositories available. As a result, demands for a vendor-agnostic, open data format for long-term archiving of NMR data have emerged with the aim to ease and encourage sharing, comparison, and reuse of NMR data. Here we present nmrML, an open XML-based exchange and storage format for NMR spectral data. The nmrML format is intended to be fully compatible with existing NMR data for chemical, biochemical, and metabolomics experiments. nmrML can capture raw NMR data, spectral data acquisition parameters, and where available spectral metadata, such as chemical structures associated with spectral assignments. The nmrML format is compatible with pure-compound NMR data for reference spectral libraries as well as NMR data from complex biomixtures, i.e., metabolomics experiments. To facilitate format conversions, we provide nmrML converters for Bruker, JEOL and Agilent/Varian vendor formats. In addition, easy-to-use Web-based spectral viewing, processing, and spectral assignment tools that read and write nmrML have been developed. Software libraries and Web services for data validation are available for tool developers and end-users. The nmrML format has already been adopted for capturing and disseminating NMR data for small molecules by several open source data processing tools and metabolomics reference spectral libraries, e.g., serving as storage format for the MetaboLights data repository. The nmrML open access data standard has been endorsed by the Metabolomics Standards Initiative (MSI), and we here encourage user participation and feedback to increase usability and make it a successful standard.


Assuntos
Bases de Dados de Compostos Químicos/normas , Espectroscopia de Ressonância Magnética/estatística & dados numéricos , Metabolômica/métodos , Software
13.
J Cheminform ; 9(1): 33, 2017 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-29086040

RESUMO

BACKGROUND: The Chemistry Development Kit (CDK) is a widely used open source cheminformatics toolkit, providing data structures to represent chemical concepts along with methods to manipulate such structures and perform computations on them. The library implements a wide variety of cheminformatics algorithms ranging from chemical structure canonicalization to molecular descriptor calculations and pharmacophore perception. It is used in drug discovery, metabolomics, and toxicology. Over the last 10 years, the code base has grown significantly, however, resulting in many complex interdependencies among components and poor performance of many algorithms. RESULTS: We report improvements to the CDK v2.0 since the v1.2 release series, specifically addressing the increased functional complexity and poor performance. We first summarize the addition of new functionality, such atom typing and molecular formula handling, and improvement to existing functionality that has led to significantly better performance for substructure searching, molecular fingerprints, and rendering of molecules. Second, we outline how the CDK has evolved with respect to quality control and the approaches we have adopted to ensure stability, including a code review mechanism. CONCLUSIONS: This paper highlights our continued efforts to provide a community driven, open source cheminformatics library, and shows that such collaborative projects can thrive over extended periods of time, resulting in a high-quality and performant library. By taking advantage of community support and contributions, we show that an open source cheminformatics project can act as a peer reviewed publishing platform for scientific computing software. Graphical abstract CDK 2.0 provides new features and improved performance.

15.
F1000Res ; 62017.
Artigo em Inglês | MEDLINE | ID: mdl-29043062

RESUMO

Metabolomics, the youngest of the major omics technologies, is supported by an active community of researchers and infrastructure developers across Europe. To coordinate and focus efforts around infrastructure building for metabolomics within Europe, a workshop on the "Future of metabolomics in ELIXIR" was organised at Frankfurt Airport in Germany. This one-day strategic workshop involved representatives of ELIXIR Nodes, members of the PhenoMeNal consortium developing an e-infrastructure that supports workflow-based metabolomics analysis pipelines, and experts from the international metabolomics community. The workshop established metabolite identification as the critical area, where a maximal impact of computational metabolomics and data management on other fields could be achieved. In particular, the existing four ELIXIR Use Cases, where the metabolomics community - both industry and academia - would benefit most, and which could be exhaustively mapped onto the current five ELIXIR Platforms were discussed. This opinion article is a call for support for a new ELIXIR metabolomics Use Case, which aligns with and complements the existing and planned ELIXIR Platforms and Use Cases.

16.
Metabolomics ; 13(9): 106, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28890673

RESUMO

INTRODUCTION: The field of metabolomics has expanded greatly over the past two decades, both as an experimental science with applications in many areas, as well as in regards to data standards and bioinformatics software tools. The diversity of experimental designs and instrumental technologies used for metabolomics has led to the need for distinct data analysis methods and the development of many software tools. OBJECTIVES: To compile a comprehensive list of the most widely used freely available software and tools that are used primarily in metabolomics. METHODS: The most widely used tools were selected for inclusion in the review by either ≥ 50 citations on Web of Science (as of 08/09/16) or the use of the tool being reported in the recent Metabolomics Society survey. Tools were then categorised by the type of instrumental data (i.e. LC-MS, GC-MS or NMR) and the functionality (i.e. pre- and post-processing, statistical analysis, workflow and other functions) they are designed for. RESULTS: A comprehensive list of the most used tools was compiled. Each tool is discussed within the context of its application domain and in relation to comparable tools of the same domain. An extended list including additional tools is available at https://github.com/RASpicer/MetabolomicsTools which is classified and searchable via a simple controlled vocabulary. CONCLUSION: This review presents the most widely used tools for metabolomics analysis, categorised based on their main functionality. As future work, we suggest a direct comparison of tools' abilities to perform specific data analysis tasks e.g. peak picking.

17.
Sci Data ; 4: 170137, 2017 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-28949328

RESUMO

The Metabolomics Standards Initiative (MSI) guidelines were first published in 2007. These guidelines provided reporting standards for all stages of metabolomics analysis: experimental design, biological context, chemical analysis and data processing. Since 2012, a series of public metabolomics databases and repositories, which accept the deposition of metabolomic datasets, have arisen. In this study, the compliance of 399 public data sets, from four major metabolomics data repositories, to the biological context MSI reporting standards was evaluated. None of the reporting standards were complied with in every publicly available study, although adherence rates varied greatly, from 0 to 97%. The plant minimum reporting standards were the most complied with and the microbial and in vitro were the least. Our results indicate the need for reassessment and revision of the existing MSI reporting standards.

18.
Gigascience ; 6(8): 1-4, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28830114

RESUMO

Following similar global efforts to exchange genomic and other biomedical data, global databases in metabolomics have now been established. MetaboLights, the first general purpose, publically available, cross-species, cross-application database in metabolomics, has become the fastest growing data repository at the European Bioinformatics Institute in terms of data volume. Here we present the automated assembly of species metabolomes in MetaboLights, a crucial reference for chemical biology, which is growing through user submissions.


Assuntos
Biologia Computacional/métodos , Bases de Dados Factuais , Metabolômica/métodos , Interface Usuário-Computador , Metaboloma , Especificidade da Espécie
20.
Bioinformatics ; 33(16): 2598-2600, 2017 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-28402395

RESUMO

Summary: Submission to the MetaboLights repository for metabolomics data currently places the burden of reporting instrument and acquisition parameters in ISA-Tab format on users, who have to do it manually, a process that is time consuming and prone to user input error. Since the large majority of these parameters are embedded in instrument raw data files, an opportunity exists to capture this metadata more accurately. Here we report a set of Python packages that can automatically generate ISA-Tab metadata file stubs from raw XML metabolomics data files. The parsing packages are separated into mzML2ISA (encompassing mzML and imzML formats) and nmrML2ISA (nmrML format only). Overall, the use of mzML2ISA & nmrML2ISA reduces the time needed to capture metadata substantially (capturing 90% of metadata on assay and sample levels), is much less prone to user input errors, improves compliance with minimum information reporting guidelines and facilitates more finely grained data exploration and querying of datasets. Availability and Implementation: mzML2ISA & nmrML2ISA are available under version 3 of the GNU General Public Licence at https://github.com/ISA-tools. Documentation is available from http://2isa.readthedocs.io/en/latest/. Contact: reza.salek@ebi.ac.uk or isatools@googlegroups.com. Supplementary information: Supplementary data are available at Bioinformatics online.


Assuntos
Armazenamento e Recuperação da Informação , Metabolômica/métodos , Metadados , Software , Mineração de Dados/métodos
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