scholarly journals Diverse Taxonomies for Diverse Chemistries: Enhanced Representation of Natural Product Metabolism in UniProtKB

Metabolites ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 48
Author(s):  
Marc Feuermann ◽  
Emmanuel Boutet ◽  
Anne Morgat ◽  
Kristian Axelsen ◽  
Parit Bansal ◽  
...  
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Semantic Web Technologies ◽  
Knowledge Resources ◽  
Web Technologies ◽  
Chemical Structures ◽  
Biological Interest ◽  
Catalyzed Reactions ◽  
Enzyme Catalyzed Reactions ◽  
Practical Demonstration

The UniProt Knowledgebase UniProtKB is a comprehensive, high-quality, and freely accessible resource of protein sequences and functional annotation that covers genomes and proteomes from tens of thousands of taxa, including a broad range of plants and microorganisms producing natural products of medical, nutritional, and agronomical interest. Here we describe work that enhances the utility of UniProtKB as a support for both the study of natural products and for their discovery. The foundation of this work is an improved representation of natural product metabolism in UniProtKB using Rhea, an expert-curated knowledgebase of biochemical reactions, that is built on the ChEBI (Chemical Entities of Biological Interest) ontology of small molecules. Knowledge of natural products and precursors is captured in ChEBI, enzyme-catalyzed reactions in Rhea, and enzymes in UniProtKB/Swiss-Prot, thereby linking chemical structure data directly to protein knowledge. We provide a practical demonstration of how users can search UniProtKB for protein knowledge relevant to natural products through interactive or programmatic queries using metabolite names and synonyms, chemical identifiers, chemical classes, and chemical structures and show how to federate UniProtKB with other data and knowledge resources and tools using semantic web technologies such as RDF and SPARQL. All UniProtKB data are freely available for download in a broad range of formats for users to further mine or exploit as an annotation source, to enrich other natural product datasets and databases.

Unzipping Natural Products: Improved Natural Product Structure Predictions by Ensemble Modeling and Fingerprint Matching

2018 ◽  
Author(s):  
William A. Shirley ◽  
Brian P. Kelley ◽  
Yohann Potier ◽  
John H. Koschwanez ◽  
Robert Bruccoleri ◽  
...  
Keyword(s):  
Natural Products ◽  
Open Source ◽  
Natural Product ◽  
Gene Cluster ◽  
Public Domain ◽  
Product Structure ◽  
Fingerprint Matching ◽  
Ensemble Modeling ◽  
Chemical Structures ◽  
Source Gene

This pre-print explores ensemble modeling of natural product targets to match chemical structures to precursors found in large open-source gene cluster repository antiSMASH. Commentary on method, effectiveness, and limitations are enclosed. All structures are public domain molecules and have been reviewed for release.

Ir-Catalyzed reactions in natural product synthesis

2018 ◽  
Vol 5 (1) ◽  
pp. 132-150 ◽  
Author(s):  
Pengquan Chen ◽  
Yuecheng Wu ◽  
Shifa Zhu ◽  
Huanfeng Jiang ◽  
Zhiqiang Ma
Keyword(s):  
Natural Products ◽  
Total Synthesis ◽  
Natural Product ◽  
Natural Product Synthesis ◽  
Catalyzed Reactions

This review highlights the recent applications of Ir-catalyzed reactions in the total synthesis of natural products.

scholarly journals All-carbon [3 + 2] cycloaddition in natural product synthesis

2020 ◽  
Vol 16 ◽  
pp. 3015-3031
Author(s):  
Zhuo Wang ◽  
Junyang Liu
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Structural Features ◽  
Single Step ◽  
Natural Product Synthesis ◽  
Synthetic Chemistry ◽  
Quaternary Centers ◽  
Chemical Structures ◽  
Quaternary Center ◽  
Medicinal Properties

Many natural products possess interesting medicinal properties that arise from their intriguing chemical structures. The highly-substituted carbocycle is one of the most common structural features in many structurally complicated natural products. However, the construction of highly-substituted, stereo-congested, five-membered carbocycles containing all-carbon quaternary center(s) is, at present, a distinct challenge in modern synthetic chemistry, which can be accessed through the all-carbon [3 + 2] cycloaddition. More importantly, the all-carbon [3 + 2] cycloaddition can forge vicinal all-carbon quaternary centers in a single step and has been demonstrated in the synthesis of complex natural products. In this review, we present the development of all-carbon [3 + 2] cycloadditions and illustrate their application in natural product synthesis reported in the last decade covering 2011–2020 (inclusive).

A Recent Look into Natural Products that have Potential to Inhibit Cholinesterases and Monoamine Oxidase B: Update for 2010-2019

2020 ◽  
Vol 23 (9) ◽  
pp. 862-876
Author(s):  
Hayrettin O. Gulcan ◽  
Ilkay E. Orhan
Keyword(s):  
Natural Products ◽  
Monoamine Oxidase ◽  
Natural Product ◽  
Biological Activities ◽  
Treatment Options ◽  
Monoamine Oxidase B ◽  
Chemical Structures ◽  
Natural Agents ◽  
Natural Product Research ◽  
Multiple Receptors

With respect to the unknowns of pathophysiology of Alzheimer’s Disease (AD)-, and Parkinson’s Disease (PD)-like neurodegenerative disorders, natural product research is still one of the valid tools in order to provide alternative and/or better treatment options. At one hand, various extracts of herbals provide a combination of actions targeting multiple receptors, on the other hand, the discovery of active natural products (i.e., secondary metabolites) generally offers alternative chemical structures either ready to be employed in clinical studies or available to be utilized as important scaffolds for the design of novel agents. Regarding the importance of certain enzymes (e.g. cholinesterase and monoamine oxidase B), for the treatment of AD and PD, we have surveyed the natural product research within this area in the last decade. Particularly novel natural agents discovered within this period, concomitant to novel biological activities displayed for known natural products, are harmonized within the present study.

scholarly journals Cheminformatics to Characterize Pharmacologically Active Natural Products

Biomolecules ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1566 ◽  
Author(s):  
José L. Medina-Franco ◽  
Fernanda I. Saldívar-González
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Natural Product ◽  
Chemical Space ◽  
Data Sets ◽  
Fragment Analysis ◽  
Chemical Structures ◽  
Speed Up ◽  
Pharmacologically Active ◽  
Design Experiments

Natural products have a significant role in drug discovery. Natural products have distinctive chemical structures that have contributed to identifying and developing drugs for different therapeutic areas. Moreover, natural products are significant sources of inspiration or starting points to develop new therapeutic agents. Natural products such as peptides and macrocycles, and other compounds with unique features represent attractive sources to address complex diseases. Computational approaches that use chemoinformatics and molecular modeling methods contribute to speed up natural product-based drug discovery. Several research groups have recently used computational methodologies to organize data, interpret results, generate and test hypotheses, filter large chemical databases before the experimental screening, and design experiments. This review discusses a broad range of chemoinformatics applications to support natural product-based drug discovery. We emphasize profiling natural product data sets in terms of diversity; complexity; acid/base; absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) properties; and fragment analysis. Novel techniques for the visual representation of the chemical space are also discussed.

scholarly journals Mining of Cyanobacterial Genomes Indicates That Plasmids Are Involved in the Production of Natural Products

2020 ◽  
Author(s):  
Rafael Popin ◽  
Danillo Alvarenga ◽  
Raquel Castelo-Branco ◽  
David Fewer ◽  
Kaarina Sivonen
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Biological Activities ◽  
Gene Clusters ◽  
Biosynthetic Pathways ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Chemical Structures ◽  
Wide Range ◽  
Genes Encoding

Abstract Background Microbial natural products have unique chemical structures and diverse biological activities. Cyanobacteria commonly possess a wide range of biosynthetic gene clusters to produce natural products. Several studies have mapped the distribution of natural product biosynthetic gene clusters in cyanobacterial genomes. However, little attention has been paid to natural product biosynthesis in plasmids. Some genes encoding cyanobacterial natural product biosynthetic pathways are believed to be dispersed by plasmids through horizontal gene transfer. Thus, we examined complete cyanobacterial genomes to assess if plasmids are involved in the production and dissemination of natural products by cyanobacteria.Results The 185 analyzed genomes possessed 1 to 42 gene clusters and an average of 10. In total, 1816 biosynthetic gene clusters were found. Approximately 95% of these clusters were present in chromosomes. The remaining 5% were present in plasmids, from which homologs of the biosynthetic pathways for aeruginosin, anabaenopeptin, ambiguine, cryptophycin, hassallidin, geosmin, and microcystin were manually curated. The cryptophycin pathway was previously described as active while the other gene cluster include all genes for biosynthesis. Approximately 12% of the 424 analyzed cyanobacterial plasmids contained homologs of genes involved in conjugation. Large plasmids, previously named as “chromids”, were also observed to be widespread in cyanobacteria. Sixteen cryptic natural product biosynthetic gene clusters and geosmin biosynthetic gene clusters were located in those mobile plasmids.Conclusion Homologues of genes involved in the production of toxins, protease inhibitors, odorous compounds, antimicrobials, antitumorals, and other unidentified natural products are located in cyanobacterial plasmids. Some of these plasmids are predicted to be conjugative. The present study provides in silico evidence that plasmids are involved in the distribution of natural product biosynthetic pathways in cyanobacteria.

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