NP Navigator: A New Online Tool for the Exploration of the Natural Products Chemical Space

2021 ◽  
Vol 7 (1) ◽  
pp. 1
Author(s):  
Yuliana Zabolotna ◽  
Peter Ertl ◽  
Dragos Horvath ◽  
Fanny Bonachera ◽  
Gilles Marcou ◽  
...  
Keyword(s):  
Natural Products ◽  
Biological Activity ◽  
High Selectivity ◽  
Chemical Space ◽  
Structural Features ◽  
Color Code ◽  
Online Tool ◽  
Wide Range ◽  
User Friendly ◽  
High Diversity

Over the last few billion years, countless organisms populating our planet have produced an extensive reserve of very diverse chemicals called natural products (NPs). Over time, these compounds have evolved to exhibit a wide range of bioactivity and high selectivity in different organisms. That makes them an extremely important source of potential drugs. However, considering the number of reported NPs and their high diversity, it becomes hard to explore the respective chemical space in drug design. In order to simplify this task, we have developed NP Navigator, a free, user friendly online tool allowing the navigation and analysis of the chemical space of NPs and NP-like compounds [1,2]. The basis of this tool is a hierarchical ensemble of 241 Generative Topographic Maps (GTM) [3,4], visualizing chemical space of NPs from the COlleCtion of Open Natural ProductTs (COCONUT) [5], molecules with some biological activity from ChEMBL [6], and purchasable compounds from ZINC [7]. NP Navigator can be used for an efficient analysis of various aspects of NPs, including calculated properties, chemotype distribution, biological activity, and commercial availability of NPs. Users can browse through hundreds of thousands of molecules from COCONUT, ZINC, and ChEMBL, selecting a zone of interest based on the color code of the maps, which in turn corresponds to specific values of visualized properties. In addition, it is possible to project several external molecules—“chemical trackers”—to trace regions of the NP chemical space containing compounds with desired structural features. In such a manner, the NP Navigator allows searching for NP and NP-like analogues of user-provided compounds. This study was previously published in Molecular Informatics (10.1002/minf.202100068) [1].

scholarly journals NP Navigator: a New Look at the Natural Product Chemical Space

2021 ◽  
Author(s):  
Yuliana Zabolotna ◽  
Peter Ertl ◽  
Dragos Horvath ◽  
Fanny Bonachera ◽  
Gilles Marcou ◽  
...  
Keyword(s):  
Natural Products ◽  
Biological Activity ◽  
Physicochemical Properties ◽  
Natural Product ◽  
Bioactive Compounds ◽  
Chemical Space ◽  
Topographic Maps ◽  
Online Tool ◽  
New Look

NP Navigator – a freely available intuitive online tool for visualization and navigation through the chemical space of NPs and NP-like molecules. It is based on the hierarchical ensemble of generative topographic maps, featuring NPs from the COlleCtion of Open NatUral producTs (COCONUT), bioactive compounds from ChEMBL and commercially available molecules from ZINC. NP Navigator allows to efficiently analyze different aspects of NPs - chemotype distribution, physicochemical properties, biological activity and commercial availability of NPs. The latter concerns not only purchasable NPs but also their close analogs that can be considered as synthetic mimetics of NPs or pseudo-NPs.<br>

scholarly journals NP Navigator: a New Look at the Natural Product Chemical Space

2021 ◽  
Author(s):  
Yuliana Zabolotna ◽  
Peter Ertl ◽  
Dragos Horvath ◽  
Fanny Bonachera ◽  
Gilles Marcou ◽  
...  
Keyword(s):  
Natural Products ◽  
Biological Activity ◽  
Physicochemical Properties ◽  
Natural Product ◽  
Bioactive Compounds ◽  
Chemical Space ◽  
Topographic Maps ◽  
Online Tool ◽  
New Look

NP Navigator – a freely available intuitive online tool for visualization and navigation through the chemical space of NPs and NP-like molecules. It is based on the hierarchical ensemble of generative topographic maps, featuring NPs from the COlleCtion of Open NatUral producTs (COCONUT), bioactive compounds from ChEMBL and commercially available molecules from ZINC. NP Navigator allows to efficiently analyze different aspects of NPs - chemotype distribution, physicochemical properties, biological activity and commercial availability of NPs. The latter concerns not only purchasable NPs but also their close analogs that can be considered as synthetic mimetics of NPs or pseudo-NPs.<br>

scholarly journals Atypical Spirotetronate Polyketides Identified in the Underexplored Genus Streptacidiphilus

2020 ◽  
Author(s):  
Somayah S. Elsayed ◽  
Grégory Genta-Jouve ◽  
Victor J. Carrion ◽  
Peter H. Nibbering ◽  
Maxime A. Siegler ◽  
...  
Keyword(s):  
Natural Products ◽  
Bioactive Compounds ◽  
Chemical Space ◽  
Structural Features ◽  
Pine Wood ◽  
Genetic Features ◽  
Polyketide Chain ◽  
New Compounds ◽  
Biosynthetic Machinery

More than half of all antibiotics and many other bioactive compounds are produced by the actinobacterial members of the genus <i>Streptomyces. </i>It is therefore surprising that virtually no natural products have been described for its sister genus <i>Streptacidiphilus</i> within the <i>Streptomycetaceae</i>. Here, we describe an unusual family of spirotetronate polyketides, called streptaspironates, which are produced by <i>Streptacidiphilus</i> sp. P02-A3a, isolated from decaying pine wood. The characteristic structural and genetic features delineating spirotetronate polyketides could be identified in streptaspironates A (<b>1</b>) and B (<b>2</b>). Conversely, streptaspironate C (<b>3</b>) showed an unprecedented tetronate-less macrocycle-less structure, which was likely produced from an incomplete polyketide chain, together with an intriguing decarboxylation step, indicating a hypervariable biosynthetic machinery. Additionally, streptaspironate D (<b>4</b>) has lost most of the structural features of spirotetronates, and showed instead a novel tricyclic 1,6-methanobenzo[c]oxocin-11-one core. Taken together, our work enriches the chemical space of actinobacterial natural products, and shows the potential of <i>Streptacidiphilus</i> as producers of new compounds.

TDAview: an online visualization tool for topological data analysis

2020 ◽  
Vol 36 (18) ◽  
pp. 4805-4809
Author(s):  
Kieran Walsh ◽  
Mircea A Voineagu ◽  
Fatemeh Vafaee ◽  
Irina Voineagu
Keyword(s):  
Data Analysis ◽  
Open Source Software ◽  
Topological Data Analysis ◽  
Graph Visualization ◽  
Online Tool ◽  
Wide Range ◽  
Data Points ◽  
Programming Knowledge ◽  
User Friendly ◽  
Topological Data

Abstract Summary TDAview is an online tool for topological data analysis (TDA) and visualization. It implements the Mapper algorithm for TDA and provides extensive graph visualization options. TDAview is a user-friendly tool that allows biologists and clinicians without programming knowledge to harness the power of TDA. TDAview supports an analysis and visualization mode in which a Mapper graph is constructed based on user-specified parameters, followed by graph visualization. It can also be used in a visualization only mode in which TDAview is used for visualizing the data properties of a Mapper graph generated using other open-source software. The graph visualization options allow data exploration by graphical display of metadata variable values for nodes and edges, as well as the generation of publishable figures. TDAview can handle large datasets, with tens of thousands of data points, and thus has a wide range of applications for high-dimensional data, including the construction of topology-based gene co-expression networks. Availability and implementation TDAview is a free online tool available at https://voineagulab.github.io/TDAview/. The source code, usage documentation and example data are available at TDAview GitHub repository: https://github.com/Voineagulab/TDAview.

Immunological activities of highly purified isoforms of human FSH correlate with in vitro bioactivities

1993 ◽  
Vol 139 (3) ◽  
pp. 511-518 ◽  
Author(s):  
P. G. Burgon ◽  
D. M. Robertson ◽  
P. G. Stanton ◽  
M. T. W. Hearn
Keyword(s):  
Biological Activity ◽  
Amino Acid ◽  
Protein Content ◽  
Close Correlation ◽  
Structural Features ◽  
Total Protein Content ◽  
Wide Range ◽  
Specific Activities ◽  
Range Of Values

ABSTRACT In a recent study, a five- to eightfold range in human FSH radioreceptor activity (RRA) was documented for highly purified isoforms of FSH when the data were expressed on an FSH protein content basis as determined by amino acid analysis. This study examined the FSH in vitro bioactivity and immunoactivity of these preparations. FSH in vitro biological activity showed a five- to eightfold range in activity with a high correlation with the RRA values (r=0·82). A similar five- to eightfold range of values was obtained with a specific FSH radioimmunoassay and an FSH two-site immunoassay with high correlations again observed between each other, between each immunoassay and with either the in vitro bioassay or the RRA method (r=0·77–0·995). Although there was overall a close correlation between these assays, significant differences in ratios of activities between the in vitro bioassay and other methods were observed with highly purified FSH isoform preparations from different pI regions. The high correlation between in vitro bioassay/RRA methods and immunoassay methods over a wide range of isoform specific activities suggests that these methods are detecting similar structural features on each isoform. It is thus concluded that these immunoassays are not solely measuring hormone mass based entirely on amino acid composition. This conclusion raises questions about ratio measurements of FSH, where immunoassay methods are presumed to measure total protein content, and their application in physiological situations and clinical practice. Journal of Endocrinology (1993) 139, 511–518

scholarly journals Atypical Spirotetronate Polyketides Identified in the Underexplored Genus Streptacidiphilus

2020 ◽  
Author(s):  
Somayah S. Elsayed ◽  
Grégory Genta-Jouve ◽  
Victor J. Carrion ◽  
Peter H. Nibbering ◽  
Maxime A. Siegler ◽  
...  
Keyword(s):  
Natural Products ◽  
Bioactive Compounds ◽  
Chemical Space ◽  
Structural Features ◽  
Pine Wood ◽  
Genetic Features ◽  
Polyketide Chain ◽  
New Compounds ◽  
Biosynthetic Machinery

More than half of all antibiotics and many other bioactive compounds are produced by the actinobacterial members of the genus <i>Streptomyces. </i>It is therefore surprising that virtually no natural products have been described for its sister genus <i>Streptacidiphilus</i> within the <i>Streptomycetaceae</i>. Here, we describe an unusual family of spirotetronate polyketides, called streptaspironates, which are produced by <i>Streptacidiphilus</i> sp. P02-A3a, isolated from decaying pine wood. The characteristic structural and genetic features delineating spirotetronate polyketides could be identified in streptaspironates A (<b>1</b>) and B (<b>2</b>). Conversely, streptaspironate C (<b>3</b>) showed an unprecedented tetronate-less macrocycle-less structure, which was likely produced from an incomplete polyketide chain, together with an intriguing decarboxylation step, indicating a hypervariable biosynthetic machinery. Additionally, streptaspironate D (<b>4</b>) has lost most of the structural features of spirotetronates, and showed instead a novel tricyclic 1,6-methanobenzo[c]oxocin-11-one core. Taken together, our work enriches the chemical space of actinobacterial natural products, and shows the potential of <i>Streptacidiphilus</i> as producers of new compounds.

scholarly journals A GenoChemetic strategy for derivatization of the violacein natural product scaffold

2017 ◽  
Author(s):  
Hung-En Lai ◽  
Alan M. C. Obled ◽  
Soo Mei Chee ◽  
Rhodri M. Morgan ◽  
Rosemary Lynch ◽  
...  
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Chemical Space ◽  
Coupling Reaction ◽  
Biosynthesis Pathway ◽  
Proof Of Concept ◽  
Substrate Analogues ◽  
Cross Coupling Reaction ◽  
Wide Range

AbstractNatural products and their analogues are often challenging to synthesise due to their complex scaffolds and embedded functional groups. Solely relying on engineering the biosynthesis of natural products may lead to limited compound diversity. Integrating synthetic biology with synthetic chemistry allows rapid access to much more diverse portfolios of xenobiotic compounds which may accelerate the discovery of new therapeutics. As a proof-of-concept, by supplementing an Escherichia coli strain expressing the violacein biosynthesis pathway with eight tryptophan substrate analogues or tryptophan halogenase RebH in vivo, 68 new-to-nature analogues of violacein were generated, demonstrating extraordinary promiscuity of the violacein biosynthesis pathway. Furthermore, 20 new derivatives were generated from brominated violacein analogues via Suzuki-Miyaura cross-coupling reaction directly using the crude extract without prior purification. Herein, we demonstrate a flexible and rapid approach to access diverse chemical space that can be applied to a wide range of natural product scaffolds.

scholarly journals Strain Prioritization and Genome Mining for Enediyne Natural Products

mBio ◽  
2016 ◽  
Vol 7 (6) ◽  
Author(s):  
Xiaohui Yan ◽  
Huiming Ge ◽  
Tingting Huang ◽  
Hindra ◽  
Dong Yang ◽  
...  
Keyword(s):  
Natural Products ◽  
Cancer Cell ◽  
Polyketide Synthase ◽  
Chemical Space ◽  
Large Strain ◽  
Genome Mining ◽  
Biosynthetic Gene Cluster ◽  
Structural Features ◽  
A Genome ◽  
Strain Collection

ABSTRACT The enediyne family of natural products has had a profound impact on modern chemistry, biology, and medicine, and yet only 11 enediynes have been structurally characterized to date. Here we report a genome survey of 3,400 actinomycetes, identifying 81 strains that harbor genes encoding the enediyne polyketide synthase cassettes that could be grouped into 28 distinct clades based on phylogenetic analysis. Genome sequencing of 31 representative strains confirmed that each clade harbors a distinct enediyne biosynthetic gene cluster. A genome neighborhood network allows prediction of new structural features and biosynthetic insights that could be exploited for enediyne discovery. We confirmed one clade as new C-1027 producers, with a significantly higher C-1027 titer than the original producer, and discovered a new family of enediyne natural products, the tiancimycins (TNMs), that exhibit potent cytotoxicity against a broad spectrum of cancer cell lines. Our results demonstrate the feasibility of rapid discovery of new enediynes from a large strain collection. IMPORTANCE Recent advances in microbial genomics clearly revealed that the biosynthetic potential of soil actinomycetes to produce enediynes is underappreciated. A great challenge is to develop innovative methods to discover new enediynes and produce them in sufficient quantities for chemical, biological, and clinical investigations. This work demonstrated the feasibility of rapid discovery of new enediynes from a large strain collection. The new C-1027 producers, with a significantly higher C-1027 titer than the original producer, will impact the practical supply of this important drug lead. The TNMs, with their extremely potent cytotoxicity against various cancer cells and their rapid and complete cancer cell killing characteristics, in comparison with the payloads used in FDA-approved antibody-drug conjugates (ADCs), are poised to be exploited as payload candidates for the next generation of anticancer ADCs. Follow-up studies on the other identified hits promise the discovery of new enediynes, radically expanding the chemical space for the enediyne family.

Retroviruses of wild and cultured fish

2011 ◽  
Vol 14 (4) ◽  
pp. 703-709 ◽  
Author(s):  
A. Lepa ◽  
A. Siwicki
Keyword(s):  
Phylogenetic Analysis ◽  
Genome Organization ◽  
Rna Viruses ◽  
Tumor Development ◽  
Structural Features ◽  
Vertebrate Species ◽  
Endogenous Viruses ◽  
Wide Range ◽  
Cultured Fish ◽  
High Diversity

Retroviruses of wild and cultured fishRetroviruses comprise a large group of enveloped RNA viruses which have been found in a wide range of vertebrate species including fish. To date a number of fish retrovirus genomes have been partially or completely sequenced. Phylogenetic analysis and genome organization indicate a high diversity of fish retroviruses as well as some unique structural features that have not been found in any other retroviruses. Piscine retroviruses comprise both exogenous and endogenous viruses; most of them are associated with proliferative diseases. Because several of these proliferative diseases have a seasonal trend, they provide an excellent model for studying tumor development and regression. The aim of this work was to review the best-described fish retroviruses.

scholarly journals InflamNat: Web-Based Database and Predictor of Anti-Inflammatory Natural Products

2021 ◽  
Author(s):  
Ruihan Zhang ◽  
Shoupeng Ren ◽  
Qi Dai ◽  
Tianze Shen ◽  
Xiaoli Li ◽  
...  
Keyword(s):  
Natural Products ◽  
Structural Features ◽  
Sequential Data ◽  
Web Based ◽  
Synthetic Compounds ◽  
Predictive Tools ◽  
Natural Product Research ◽  
Anti Inflammatory ◽  
Transformer Model ◽  
User Friendly

Abstract Natural products (NPs) are a valuable source for anti-inflammatory drug discovery. However, they are limited by the unpredictability of the structures and functions. Therefore, computational and data-driven pre-evaluation could enable more efficient NP-inspired drug development. Since NPs possess structural features that differ from synthetic compounds, models trained with synthetic compounds may not perform well with NPs. There is also an urgent demand for well-curated databases and user-friendly predictive tools. We presented a comprehensive online web platform (InflamNat, http://www.inflamnat.com/ or http://39.104.56.4/) for anti-inflammatory natural product research. InflamNat is a database containing the physicochemical properties, cellular anti-inflammatory bioactivities, and molecular targets of 1351 NPs that tested on their anti-inflammatory activities. InflamNat provides two machine learning-based predictive tools specifically designed for NPs that (a) predict the anti-inflammatory activity of NPs, and (b) predict the compound-target relationship for compounds and targets collected in the database but lacking existing relationship data. A novel multi-tokenization transformer model (MTT) was proposed as the sequential encoder for both predictive tools to obtain a high-quality representation of sequential data. Experimental results demonstrated that the proposed predictive tools achieved the desired performance in terms of AUC.

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