scholarly journals Leveraging orthogonal mass spectrometry based strategies for comprehensive sequencing and characterization of ribosomal antimicrobial peptide natural products

2020 ◽  
Author(s):  
Tessa B. Moyer ◽  
Nicole C. Parsley ◽  
Patric W. Sadecki ◽  
Wyatt J. Schug ◽  
Leslie M. Hicks

Strategies to accelerate natural product peptide characterization.

mSystems ◽  
2018 ◽  
Vol 3 (2) ◽  
Author(s):  
Daniela B. B. Trivella ◽  
Rafael de Felicio

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.


2013 ◽  
Vol 52 (19) ◽  
pp. 5171-5174 ◽  
Author(s):  
Susanne Holzhauser ◽  
Anja Freiwald ◽  
Christoph Weise ◽  
Gerd Multhaup ◽  
Chung-Ting Han ◽  
...  

2009 ◽  
pp. n/a-n/a ◽  
Author(s):  
Ka-Wing Cheng ◽  
Chi-Chun Wong ◽  
Mingfu Wang ◽  
Qing-Yu He ◽  
Feng Chen

2021 ◽  
Author(s):  
Giang Nguyen ◽  
Jack Bennett ◽  
Sherrie Liu ◽  
Sarah Hancock ◽  
Daniel Winter ◽  
...  

The structural diversity of natural products offers unique opportunities for drug discovery, but challenges associated with their isolation and screening can hinder the identification of drug-like molecules from complex natural product extracts. Here we introduce a mass spectrometry-based approach that integrates untargeted metabolomics with multistage, high-resolution native mass spectrometry to rapidly identify natural products that bind to therapeutically relevant protein targets. By directly screening crude natural product extracts containing thousands of drug-like small molecules using a single, rapid measurement, novel natural product ligands of human drug targets could be identified without fractionation. This method should significantly increase the efficiency of target-based natural product drug discovery workflows.


2019 ◽  
Vol 112 ◽  
pp. 87-101 ◽  
Author(s):  
Gerardo Alvarez-Rivera ◽  
Diego Ballesteros-Vivas ◽  
Fabian Parada-Alfonso ◽  
Elena Ibañez ◽  
Alejandro Cifuentes

2021 ◽  
Author(s):  
Giang Nguyen ◽  
Jack Bennett ◽  
Sherrie Liu ◽  
Sarah Hancock ◽  
Daniel Winter ◽  
...  

The structural diversity of natural products offers unique opportunities for drug discovery, but challenges associated with their isolation and screening can hinder the identification of drug-like molecules from complex natural product extracts. Here we introduce a mass spectrometry-based approach that integrates untargeted metabolomics with multistage, high-resolution native mass spectrometry to rapidly identify natural products that bind to therapeutically relevant protein targets. By directly screening crude natural product extracts containing thousands of drug-like small molecules using a single, rapid measurement, novel natural product ligands of human drug targets could be identified without fractionation. This method should significantly increase the efficiency of target-based natural product drug discovery workflows.


2016 ◽  
Vol 33 (3) ◽  
pp. 432-455 ◽  
Author(s):  
Daniel P. Demarque ◽  
Antonio E. M. Crotti ◽  
Ricardo Vessecchi ◽  
João L. C. Lopes ◽  
Norberto P. Lopes

This review article explores the most common fragmentation reactions for ions generated by ESI in positive and negative modes.


Marine Drugs ◽  
2021 ◽  
Vol 19 (1) ◽  
pp. 20
Author(s):  
Tiago Leão ◽  
Mingxun Wang ◽  
Nathan Moss ◽  
Ricardo da Silva ◽  
Jon Sanders ◽  
...  

Microbial natural products are important for the understanding of microbial interactions, chemical defense and communication, and have also served as an inspirational source for numerous pharmaceutical drugs. Tropical marine cyanobacteria have been highlighted as a great source of new natural products, however, few reports have appeared wherein a multi-omics approach has been used to study their natural products potential (i.e., reports are often focused on an individual natural product and its biosynthesis). This study focuses on describing the natural product genetic potential as well as the expressed natural product molecules in benthic tropical cyanobacteria. We collected from several sites around the world and sequenced the genomes of 24 tropical filamentous marine cyanobacteria. The informatics program antiSMASH was used to annotate the major classes of gene clusters. BiG-SCAPE phylum-wide analysis revealed the most promising strains for natural product discovery among these cyanobacteria. LCMS/MS-based metabolomics highlighted the most abundant molecules and molecular classes among 10 of these marine cyanobacterial samples. We observed that despite many genes encoding for peptidic natural products, peptides were not as abundant as lipids and lipopeptides in the chemical extracts. Our results highlight a number of highly interesting biosynthetic gene clusters for genome mining among these cyanobacterial samples.


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