ChemInform Abstract: Genome Mining for Novel Natural Product Discovery

ChemInform ◽  
2008 ◽  
Vol 39 (29) ◽  
Author(s):  
Gregory L. Challis
Keyword(s):  
Natural Product ◽  
Genome Mining ◽  
Natural Product Discovery

scholarly journals The Tripod for Bacterial Natural Product Discovery: Genome Mining, Silent Pathway Induction, and Mass Spectrometry-Based Molecular Networking

mSystems ◽  
2018 ◽  
Vol 3 (2) ◽  
Author(s):  
Daniela B. B. Trivella ◽  
Rafael de Felicio
Keyword(s):  
Mass Spectrometry ◽  
Natural Products ◽  
Natural Product ◽  
Biosynthetic Pathway ◽  
Genome Mining ◽  
Chemical Compounds ◽  
Gene Clusters ◽  
Tandem Mass ◽  
Molecular Networking ◽  
Natural Product Discovery

ABSTRACT Natural products are the richest source of chemical compounds for drug discovery. Particularly, bacterial secondary metabolites are in the spotlight due to advances in genome sequencing and mining, as well as for the potential of biosynthetic pathway manipulation to awake silent (cryptic) gene clusters under laboratory cultivation. Further progress in compound detection, such as the development of the tandem mass spectrometry (MS/MS) molecular networking approach, has contributed to the discovery of novel bacterial natural products. The latter can be applied directly to bacterial crude extracts for identifying and dereplicating known compounds, therefore assisting the prioritization of extracts containing novel natural products, for example. In our opinion, these three approaches—genome mining, silent pathway induction, and MS-based molecular networking—compose the tripod for modern bacterial natural product discovery and will be discussed in this perspective.

Natural product discovery through microbial genome mining

2021 ◽  
Vol 60 ◽  
pp. 47-54
Author(s):  
Emma Kenshole ◽  
Marion Herisse ◽  
Michael Michael ◽  
Sacha J. Pidot
Keyword(s):  
Natural Product ◽  
Genome Mining ◽  
Microbial Genome ◽  
Natural Product Discovery

scholarly journals Genomic Assemblies of Members of Burkholderia and Related Genera as a Resource for Natural Product Discovery

2020 ◽  
Vol 9 (42) ◽  
Author(s):  
Alex J. Mullins ◽  
Cerith Jones ◽  
Matthew J. Bull ◽  
Gordon Webster ◽  
Julian Parkhill ◽  
...  
Keyword(s):  
Natural Product ◽  
Genome Mining ◽  
Genomic Analysis ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Natural Product Discovery

ABSTRACT The genomes of 450 members of Burkholderiaceae, isolated from clinical and environmental sources, were sequenced and assembled as a resource for genome mining. Genomic analysis of the collection has enabled the identification of multiple metabolites and their biosynthetic gene clusters, including the antibiotics gladiolin, icosalide A, enacyloxin, and cepacin A.

scholarly journals Omics-based natural product discovery and the lexicon of genome mining

2017 ◽  
Vol 39 ◽  
pp. 136-142 ◽  
Author(s):  
Henrique Machado ◽  
Robert N Tuttle ◽  
Paul R Jensen
Keyword(s):  
Natural Product ◽  
Genome Mining ◽  
Natural Product Discovery

Structural Determination of an Orphan Natural Product Using Microcrystal Electron Diffraction and Genome Mining

2020 ◽  
Author(s):  
Lee Joon Kim ◽  
Masao Ohashi ◽  
Dan Tan ◽  
Matthew Asay ◽  
Duilio Cascio ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Electron Diffraction ◽  
Natural Product ◽  
Genome Mining ◽  
Precise Determination ◽  
New Drugs ◽  
Structural Determination ◽  
Natural Product Discovery ◽  
Living Organisms

<p>More than 60% of pharmaceuticals are related to natural products (NPs), chemicals produced by living organisms.<a></a> Hence, new methods that accelerate natural product discovery are poised to profoundly impact human health. Of the many challenges that remain in natural product discovery, none are as pervasive as structural elucidation, as determination of the molecular structure of a newly discovered natural product can take months, years, or in some cases be altogether unachievable. This challenge can be fueled by lack of sufficient material for spectroscopic analysis, or difficulties in sourcing the producing organism. Even in cases where the analyte is abundant, its physical properties, including molecular structure, can prevent unambiguous structural determination. Here we report the use of microcrystal electron diffraction (MicroED),<a></a> an emerging cryogenic electron microscopy (CryoEM) technique, in combination with genome mining, to address these challenges. As proof-of-principle, we apply these techniques to fischerin (<b>1</b>), an orphan NP isolated more than 30 years ago, with potent cytotoxicity but ambiguous structural assignment.<a></a> We utilize genome mining methods to reconstruct its biosynthetic pathway and highlight the sensitivity of MicroED through the precise determination of the solid-state structure of <b>1</b> from sub-micron thick crystals. This structural solution serves as a powerful demonstration of the synergy of MicroED and synthetic biology in NP discovery, technologies that when taken together will ultimately accelerate the rate at which new drugs are discovered.</p><div><div><p> </p></div></div>

scholarly journals BiG-SLiCE: A Highly Scalable Tool Maps the Diversity of 1.2 Million Biosynthetic Gene Clusters

2020 ◽  
Author(s):  
Satria A. Kautsar ◽  
Justin J. J. van der Hooft ◽  
Dick de Ridder ◽  
Marnix H. Medema
Keyword(s):  
Natural Product ◽  
Biological Activities ◽  
Genome Mining ◽  
Gene Clusters ◽  
Genomic Diversity ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Microbial Genomes ◽  
Natural Product Discovery ◽  
User Friendly

AbstractBackgroundGenome mining for Biosynthetic Gene Clusters (BGCs) has become an integral part of natural product discovery. The >200,000 microbial genomes now publicly available hold information on abundant novel chemistry. One way to navigate this vast genomic diversity is through comparative analysis of homologous BGCs, which allows identification of cross-species patterns that can be matched to the presence of metabolites or biological activities. However, current tools suffer from a bottleneck caused by the expensive network-based approach used to group these BGCs into Gene Cluster Families (GCFs).ResultsHere, we introduce BiG-SLiCE, a tool designed to cluster massive numbers of BGCs. By representing them in Euclidean space, BiG-SLiCE can group BGCs into GCFs in a non-pairwise, near-linear fashion. We used BiG-SLiCE to analyze 1,225,071 BGCs collected from 209,206 publicly available microbial genomes and metagenome-assembled genomes (MAGs) within ten days on a typical 36-cores CPU server. We demonstrate the utility of such analyses by reconstructing a global map of secondary metabolic diversity across taxonomy to identify uncharted biosynthetic potential. BiG-SLiCE also provides a "query mode" that can efficiently place newly sequenced BGCs into previously computed GCFs, plus a powerful output visualization engine that facilitates user-friendly data exploration.ConclusionsBiG-SLiCE opens up new possibilities to accelerate natural product discovery and offers a first step towards constructing a global, searchable interconnected network of BGCs. As more genomes get sequenced from understudied taxa, more information can be mined to highlight their potentially novel chemistry. BiG-SLiCE is available via https://github.com/medema-group/bigslice.

Structural Determination of an Orphan Natural Product Using Microcrystal Electron Diffraction and Genome Mining

2020 ◽  
Author(s):  
Lee Joon Kim ◽  
Masao Ohashi ◽  
Dan Tan ◽  
Matthew Asay ◽  
Duilio Cascio ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Electron Diffraction ◽  
Natural Product ◽  
Genome Mining ◽  
Precise Determination ◽  
New Drugs ◽  
Structural Determination ◽  
Natural Product Discovery ◽  
Living Organisms

<p>More than 60% of pharmaceuticals are related to natural products (NPs), chemicals produced by living organisms.<a></a> Hence, new methods that accelerate natural product discovery are poised to profoundly impact human health. Of the many challenges that remain in natural product discovery, none are as pervasive as structural elucidation, as determination of the molecular structure of a newly discovered natural product can take months, years, or in some cases be altogether unachievable. This challenge can be fueled by lack of sufficient material for spectroscopic analysis, or difficulties in sourcing the producing organism. Even in cases where the analyte is abundant, its physical properties, including molecular structure, can prevent unambiguous structural determination. Here we report the use of microcrystal electron diffraction (MicroED),<a></a> an emerging cryogenic electron microscopy (CryoEM) technique, in combination with genome mining, to address these challenges. As proof-of-principle, we apply these techniques to fischerin (<b>1</b>), an orphan NP isolated more than 30 years ago, with potent cytotoxicity but ambiguous structural assignment.<a></a> We utilize genome mining methods to reconstruct its biosynthetic pathway and highlight the sensitivity of MicroED through the precise determination of the solid-state structure of <b>1</b> from sub-micron thick crystals. This structural solution serves as a powerful demonstration of the synergy of MicroED and synthetic biology in NP discovery, technologies that when taken together will ultimately accelerate the rate at which new drugs are discovered.</p><div><div><p> </p></div></div>

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