Discovering New Natural Products Using Metabolomics-Based Approaches

Overview

Journal Adv Exp Med Biol

Specialties Biology
General Medicine

Date 2023 Oct 16

PMID 37843810

Authors

Livia Soman de Medeiros

Moyses B de Araujo Junior

Eldrinei G Peres

Jose Carlos Ipuchima da Silva

Milena Costa Bassicheto

Giordanno Di Gioia

Thiago Andre Moura Veiga

Hector Henrique Ferreira Koolen

Affiliations

Soon will be listed here.

Abstract

The incessant search for new natural molecules with biological activities has forced researchers in the field of chemistry of natural products to seek different approaches for their prospection studies. In particular, researchers around the world are turning to approaches in metabolomics to avoid high rates of re-isolation of certain compounds, something recurrent in this branch of science. Thanks to the development of new technologies in the analytical instrumentation of spectroscopic and spectrometric techniques, as well as the advance in the computational processing modes of the results, metabolomics has been gaining more and more space in studies that involve the prospection of natural products. Thus, this chapter summarizes the precepts and good practices in the metabolomics of microbial natural products using mass spectrometry and nuclear magnetic resonance spectroscopy, and also summarizes several examples where this approach has been applied in the discovery of bioactive molecules.

Citing Articles

Editorial: Harmonization of protocols investigating natural products: the role of chemical analysis from studies to clinical research.

Haznedaroglu M, Menghini L, Gokce G, Gokbulut A Front Pharmacol. 2024; 15:1490109.

PMID: 39534087 PMC: 11555292. DOI: 10.3389/fphar.2024.1490109.

Metabonomic analysis to identify exometabolome changes underlying antifungal and growth promotion mechanisms of endophytic Actinobacterium for sustainable agriculture practice.

Mohamad O, Liu Y, Huang Y, Kuchkarova N, Dong L, Jiao J Front Microbiol. 2024; 15:1439798.

PMID: 39282566 PMC: 11393692. DOI: 10.3389/fmicb.2024.1439798.

References

Kjaerbolling I, Mortensen U, Vesth T, Andersen M . Strategies to establish the link between biosynthetic gene clusters and secondary metabolites. Fungal Genet Biol. 2019; 130:107-121. DOI: 10.1016/j.fgb.2019.06.001. View

Ramirez-Rendon D, Passari A, Ruiz-Villafan B, Rodriguez-Sanoja R, Sanchez S, Demain A . Impact of novel microbial secondary metabolites on the pharma industry. Appl Microbiol Biotechnol. 2022; 106(5-6):1855-1878. PMC: 8860141. DOI: 10.1007/s00253-022-11821-5. View

Gruber-Dorninger C, Novak B, Nagl V, Berthiller F . Emerging Mycotoxins: Beyond Traditionally Determined Food Contaminants. J Agric Food Chem. 2016; 65(33):7052-7070. DOI: 10.1021/acs.jafc.6b03413. View

Caesar L, Kellogg J, Kvalheim O, Cech N . Opportunities and Limitations for Untargeted Mass Spectrometry Metabolomics to Identify Biologically Active Constituents in Complex Natural Product Mixtures. J Nat Prod. 2019; 82(3):469-484. PMC: 6837904. DOI: 10.1021/acs.jnatprod.9b00176. View

Wolfender J, Nuzillard J, van der Hooft J, Renault J, Bertrand S . Accelerating Metabolite Identification in Natural Product Research: Toward an Ideal Combination of Liquid Chromatography-High-Resolution Tandem Mass Spectrometry and NMR Profiling, in Silico Databases, and Chemometrics. Anal Chem. 2018; 91(1):704-742. DOI: 10.1021/acs.analchem.8b05112. View

Wakefield J, Hassan H, Jaspars M, Ebel R, Rateb M . Dual Induction of New Microbial Secondary Metabolites by Fungal Bacterial Co-cultivation. Front Microbiol. 2017; 8:1284. PMC: 5504103. DOI: 10.3389/fmicb.2017.01284. View

Thornburg C, Britt J, Evans J, Akee R, Whitt J, Trinh S . NCI Program for Natural Product Discovery: A Publicly-Accessible Library of Natural Product Fractions for High-Throughput Screening. ACS Chem Biol. 2018; 13(9):2484-2497. PMC: 8130845. DOI: 10.1021/acschembio.8b00389. View

Reher R, Kim H, Zhang C, Mao H, Wang M, Nothias L . A Convolutional Neural Network-Based Approach for the Rapid Annotation of Molecularly Diverse Natural Products. J Am Chem Soc. 2020; 142(9):4114-4120. PMC: 7210566. DOI: 10.1021/jacs.9b13786. View

Misra B, van der Hooft J . Updates in metabolomics tools and resources: 2014-2015. Electrophoresis. 2015; 37(1):86-110. DOI: 10.1002/elps.201500417. View

10.

Allard P, Genta-Jouve G, Wolfender J . Deep metabolome annotation in natural products research: towards a virtuous cycle in metabolite identification. Curr Opin Chem Biol. 2017; 36:40-49. DOI: 10.1016/j.cbpa.2016.12.022. View

11.

Caesar L, Cech N . Synergy and antagonism in natural product extracts: when 1 + 1 does not equal 2. Nat Prod Rep. 2019; 36(6):869-888. PMC: 6820002. DOI: 10.1039/c9np00011a. View

12.

Palaniappan K, Chen I, Chu K, Ratner A, Seshadri R, Kyrpides N . IMG-ABC v.5.0: an update to the IMG/Atlas of Biosynthetic Gene Clusters Knowledgebase. Nucleic Acids Res. 2019; 48(D1):D422-D430. PMC: 7145673. DOI: 10.1093/nar/gkz932. View

13.

Hautbergue T, Jamin E, Debrauwer L, Puel O, Oswald I . From genomics to metabolomics, moving toward an integrated strategy for the discovery of fungal secondary metabolites. Nat Prod Rep. 2018; 35(2):147-173. DOI: 10.1039/c7np00032d. View

14.

Gross H . Strategies to unravel the function of orphan biosynthesis pathways: recent examples and future prospects. Appl Microbiol Biotechnol. 2007; 75(2):267-77. DOI: 10.1007/s00253-007-0900-5. View

15.

Bode H, Bethe B, Hofs R, Zeeck A . Big effects from small changes: possible ways to explore nature's chemical diversity. Chembiochem. 2002; 3(7):619-27. DOI: 10.1002/1439-7633(20020703)3:7<619::AID-CBIC619>3.0.CO;2-9. View

16.

Zhang X, Hindra , Elliot M . Unlocking the trove of metabolic treasures: activating silent biosynthetic gene clusters in bacteria and fungi. Curr Opin Microbiol. 2019; 51:9-15. DOI: 10.1016/j.mib.2019.03.003. View

17.

Luo Y, Cobb R, Zhao H . Recent advances in natural product discovery. Curr Opin Biotechnol. 2014; 30:230-7. PMC: 4253731. DOI: 10.1016/j.copbio.2014.09.002. View

18.

Pfannenstiel B, Keller N . On top of biosynthetic gene clusters: How epigenetic machinery influences secondary metabolism in fungi. Biotechnol Adv. 2019; 37(6):107345. PMC: 6685777. DOI: 10.1016/j.biotechadv.2019.02.001. View

19.

Baral B, Akhgari A, Metsa-Ketela M . Activation of microbial secondary metabolic pathways: Avenues and challenges. Synth Syst Biotechnol. 2018; 3(3):163-178. PMC: 6190515. DOI: 10.1016/j.synbio.2018.09.001. View

20.

Mattern D, Valiante V, Unkles S, Brakhage A . Synthetic biology of fungal natural products. Front Microbiol. 2015; 6:775. PMC: 4519758. DOI: 10.3389/fmicb.2015.00775. View