Innovative omics-based approaches for prioritisation and targeted isolation of natural products – new strategies for drug discovery

Wolfender, Jean‐Luc; Litaudon, Marc; Touboul, David; Queiroz, Emerson Ferreira

doi:10.1039/c9np00004f

Cited by 138 publications

(125 citation statements)

References 72 publications

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“…3 However, the focus on bioactivity as selection criterion provides a biased perspective on a small portion of the chemical diversity microbes are capable to produce. Despite decades of research, the majority of secondary metabolites remain "metabolomic dark matter", 4 with high probability of structural novelty 5 and novel bioactive scaffolds. 6 Still, streamlined approaches for strain prioritization and workflow optimization are needed to render drug discovery from microbial sources a cost-effective endeavor.…”

Section: Introductionmentioning

confidence: 99%

“…6 Still, streamlined approaches for strain prioritization and workflow optimization are needed to render drug discovery from microbial sources a cost-effective endeavor. 5 Recent advances in genome mining have enabled researchers to investigate the biosynthetic potential of bacteria in silico, with minimal wet lab work. 7 Tools such as antiSMASH 8 allow to mine genomes for biosynthetic gene clusters (BGC), while BGC repositories such as MIBiG 9 aid in the evaluation of BGC novelty.…”

Section: Introductionmentioning

confidence: 99%

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Planomonospora: a Metabolomics Perspective on an Underexplored Actinobacteria Genus

Zdouc

Iorio²,

Maffioli³

et al. 2020

Preprint

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Despite an excellent track record, microbial drug discovery suffers from high rates of re-discovery. Better workflows for the rapid investigation of complex extracts are needed to increase throughput and allow early prioritization of samples. In addition, systematic characterization of poorly explored strains is seldomly performed. Here, we report a metabolomic study of 72 isolates belonging to the rare actinomycete genus Planomonospora, using a workflow of open access tools to investigate its secondary metabolites. The results reveal a correlation of chemical diversity and strain phylogeny, with classes of metabolites exclusive to certain phylogroups. We were able to identify previously reported Planomonospora metabolites, including the ureylene-containing oligopeptide antipain, the thiopeptide siomycin including new congeners and the ribosomally synthesized peptides sphaericin and lantibiotic 97518. In addition, we found that Planomonospora strains can produce the siderophore desferrioxamine or a salinichelin-like peptide. Analysis of the genomes of three newly sequenced strains led to the detection of 47 gene cluster families, of which several were connected to products found by LC-MS/MS profiling. This study demonstrates the value of metabolomic studies to investigate poorly explored taxa and provides a first picture of the biosynthetic capabilities of the genus Planomonospora.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Planomonospora: a Metabolomics Perspective on an Underexplored Actinobacteria Genus

Zdouc

Iorio²,

Maffioli³

et al. 2020

Preprint

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show abstract

“…e t a l . , 2 0 1 9 ) , a n d n e w multiinformational-based profiling approaches integrating taxonomic or bioactivity data (Wolfender et al, 2019), which would present additional techniques by which new compounds can be discovered.…”

Section: The Combining Rule and Synergy Effects Of Hps And Prescriptionsmentioning

confidence: 99%

Modular Characteristics and Mechanism of Action of Herbs for Endometriosis Treatment in Chinese Medicine: A Data Mining and Network Pharmacology–Based Identification

Zheng

et al. 2020

Front. Pharmacol.

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could also regulate VEGF signaling, toll-like reporter signaling, NF-kB signaling, MAPK signaling, PI3K-Akt signaling, and the HIF-1 signaling pathway, among others. Synergies often exist in herb pairs and herbal prescriptions. In conclusion, we identified some important targets, target pairs, and regulatory networks, using bioinformatics and data mining. The combination of data mining and network pharmacology may offer an efficient method for drug discovery and development from herbal medicines.

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“…Constituted as a powerful tool, "omics" approaches as metagenomics and genomics effectively support ecological and bioprospecting studies deciphering new insights into halophilic microorganisms [90][91][92]. Extremely rare is the interdomain horizontal gene transfer (IHGT) across bacteria, archaea, and fungi of homologous DNA.…”

Section: Archaeamentioning

confidence: 99%

Halophiles and Their Biomolecules: Recent Advances and Future Applications in Biomedicine

2019

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The organisms thriving under extreme conditions better than any other organism living on Earth, fascinate by their hostile growing parameters, physiological features, and their production of valuable bioactive metabolites. This is the case of microorganisms (bacteria, archaea, and fungi) that grow optimally at high salinities and are able to produce biomolecules of pharmaceutical interest for therapeutic applications. As along as the microbiota is being approached by massive sequencing, novel insights are revealing the environmental conditions on which the compounds are produced in the microbial community without more stress than sharing the same substratum with their peers, the salt. In this review are reported the molecules described and produced by halophilic microorganisms with a spectrum of action in vitro: antimicrobial and anticancer. The action mechanisms of these molecules, the urgent need to introduce alternative lead compounds and the current aspects on the exploitation and its limitations are discussed.

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Innovative omics-based approaches for prioritisation and targeted isolation of natural products – new strategies for drug discovery

Abstract: This review focuses on innovative omics approaches related to the prioritisation of natural extracts, to selection of efficient producing strains and to the targeted isolation of their bioactive constituents.

Cited by 138 publications

References 72 publications

Planomonospora: a Metabolomics Perspective on an Underexplored Actinobacteria Genus

Planomonospora: a Metabolomics Perspective on an Underexplored Actinobacteria Genus

Modular Characteristics and Mechanism of Action of Herbs for Endometriosis Treatment in Chinese Medicine: A Data Mining and Network Pharmacology–Based Identification

Halophiles and Their Biomolecules: Recent Advances and Future Applications in Biomedicine

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