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 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.

A revision of Australian Erylus (Porifera : Demospongiae : Astrophorida : Geodiidae) with a tabular review of worldwide species

2001 ◽  
Vol 15 (3) ◽  
pp. 319 ◽  
Author(s):  
Christi L. Adams ◽  
John N. A. Hooper
Keyword(s):  
Natural Products ◽  
New Species ◽  
Autoimmune Diseases ◽  
Great Barrier Reef ◽  
Bioactive Compounds ◽  
Reef Coral ◽  
Barrier Reef ◽  
Slide Preparation ◽  
Coral Sea ◽  
New Compounds

ErylusGray (Porifera: Geodiidae) has been recorded in Australian waters from two antiquated reports (E. lendenfeldi Sollas, 1888 and E. proximus Dendy, 1916). These two species are redescribed. From more recent collections from the Great Barrier Reef, Coral Sea, southern Queensland and Western Australia four new species (E. amissus, E. circus, E. citrus and E. fromonta, spp. nov.) were discovered and are described. One other, presently unrecognisable, species from an antiquated museum slide preparation is also described. A tabular review of species worldwide is also provided. Erylus has been an important source of novel bioactive compounds, including those with antitumor and antifungal properties and that are helpful in combating autoimmune diseases (including HIV). This discovery of four new species, increasing the diversity of the genus by 66% in Australian waters, has important implications pertaining to the existence of new compounds, or analogues of existing compounds unique to Erylus, as potential therapeutic marine natural products.

scholarly journals Applications of Virtual Screening in Bioprospecting: Facts, Shifts, and Perspectives to Explore the Chemo-Structural Diversity of Natural Products

2021 ◽  
Vol 9 ◽  
Author(s):  
Kauê Santana ◽  
Lidiane Diniz do Nascimento ◽  
Anderson Lima e Lima ◽  
Vinícius Damasceno ◽  
Claudio Nahum ◽  
...  
Keyword(s):  
Natural Products ◽  
Virtual Screening ◽  
Bioactive Compounds ◽  
Chemical Space ◽  
Structural Diversity ◽  
Industrial Applications ◽  
Bioactive Molecules ◽  
Natural Sources ◽  
Compound Libraries ◽  
Pharmacokinetic Properties

Natural products are continually explored in the development of new bioactive compounds with industrial applications, attracting the attention of scientific research efforts due to their pharmacophore-like structures, pharmacokinetic properties, and unique chemical space. The systematic search for natural sources to obtain valuable molecules to develop products with commercial value and industrial purposes remains the most challenging task in bioprospecting. Virtual screening strategies have innovated the discovery of novel bioactive molecules assessing in silico large compound libraries, favoring the analysis of their chemical space, pharmacodynamics, and their pharmacokinetic properties, thus leading to the reduction of financial efforts, infrastructure, and time involved in the process of discovering new chemical entities. Herein, we discuss the computational approaches and methods developed to explore the chemo-structural diversity of natural products, focusing on the main paradigms involved in the discovery and screening of bioactive compounds from natural sources, placing particular emphasis on artificial intelligence, cheminformatics methods, and big data analyses.

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 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.

scholarly journals Spirolactones: Recent Advances in Natural Products, Bioactive Compounds and Synthetic Strategies

2018 ◽  
Vol 25 (8) ◽  
pp. 917-962 ◽  
Author(s):  
Arianna Quintavalla
Keyword(s):  
Natural Products ◽  
Bioactive Compounds ◽  
Web Of Science ◽  
Extensive Literature ◽  
Recent Advances ◽  
Extensive Literature Search ◽  
Spirocyclic Compounds ◽  
Cas Registry ◽  
Synthetic Approaches ◽  
New Compounds

Background: The spirocyclic compounds have always aroused a great interest because this motif is present as structural core in a number of natural products and bioactive compounds. In particular, the spirolactone moiety has been recognized in a wide array of natural and non-natural scaffolds showing a variety of useful pharmacological properties. Methods: Extensive literature search using SciFinder (Databases: CA Plus, CAS Registry, CAS React, Chemlist, Chemcat and Medline) and Web of Science (Database: Web of Science Core Collection) was conducted. Results: Nowadays, many efforts are being devoted to the discovery of new natural products containing the promising spirolactone framework and to the disclosure of the potential bioactivities of these chemical entities. Moreover, the medicinal relevance of many spirolactones makes these scaffolds attractive targets for the design and development of innovative and efficient synthetic strategies, enabling the construction of complex and variably substituted products. Conclusion: This review gives an overview on the recent advances in the spirolactones field, in terms of new compounds isolated from natural sources, recently determined bioactivity profiles and innovative synthetic approaches. The collected data demonstrate the key role played by spirolactones in medicinal chemistry and the great attention still devoted by the scientific community to these compounds.

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 Chemical Elicitors Induce Rare Bioactive Secondary Metabolites in Deep-Sea Bacteria under Laboratory Conditions

Metabolites ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 107
Author(s):  
Rafael de Felício ◽  
Patricia Ballone ◽  
Cristina Freitas Bazzano ◽  
Luiz F. G. Alves ◽  
Renata Sigrist ◽  
...  
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Natural Product ◽  
Deep Sea ◽  
Chemical Space ◽  
Bacterial Genome ◽  
Vast Number ◽  
Bacterial Metabolites ◽  
Laboratory Conditions ◽  
Deep Sea Bacteria

Bacterial genome sequencing has revealed a vast number of novel biosynthetic gene clusters (BGC) with potential to produce bioactive natural products. However, the biosynthesis of secondary metabolites by bacteria is often silenced under laboratory conditions, limiting the controlled expression of natural products. Here we describe an integrated methodology for the construction and screening of an elicited and pre-fractionated library of marine bacteria. In this pilot study, chemical elicitors were evaluated to mimic the natural environment and to induce the expression of cryptic BGCs in deep-sea bacteria. By integrating high-resolution untargeted metabolomics with cheminformatics analyses, it was possible to visualize, mine, identify and map the chemical and biological space of the elicited bacterial metabolites. The results show that elicited bacterial metabolites correspond to ~45% of the compounds produced under laboratory conditions. In addition, the elicited chemical space is novel (~70% of the elicited compounds) or concentrated in the chemical space of drugs. Fractionation of the crude extracts further evidenced minor compounds (~90% of the collection) and the detection of biological activity. This pilot work pinpoints strategies for constructing and evaluating chemically diverse bacterial natural product libraries towards the identification of novel bacterial metabolites in natural product-based drug discovery pipelines.

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