Coupling Mass Spectral and Genomic Information to Improve Bacterial Natural Product Discovery Workflows

Overview

Journal Mar Drugs

Publisher MDPI

Specialties Biology
Pharmacology

Date 2021 Apr 3

PMID 33807702

Citations 6

Authors

Max Crusemann

Affiliations

Soon will be listed here.

Abstract

Bacterial natural products possess potent bioactivities and high structural diversity and are typically encoded in biosynthetic gene clusters. Traditional natural product discovery approaches rely on UV- and bioassay-guided fractionation and are limited in terms of dereplication. Recent advances in mass spectrometry, sequencing and bioinformatics have led to large-scale accumulation of genomic and mass spectral data that is increasingly used for signature-based or correlation-based mass spectrometry genome mining approaches that enable rapid linking of metabolomic and genomic information to accelerate and rationalize natural product discovery. In this mini-review, these approaches are presented, and discovery examples provided. Finally, future opportunities and challenges for paired omics-based natural products discovery workflows are discussed.

Citing Articles

Advanced Methods for Natural Products Discovery: Bioactivity Screening, Dereplication, Metabolomics Profiling, Genomic Sequencing, Databases and Informatic Tools, and Structure Elucidation.

Gaudencio S, Bayram E, Lukic Bilela L, Cueto M, Diaz-Marrero A, Haznedaroglu B Mar Drugs. 2023; 21(5).

PMID: 37233502 PMC: 10222211. DOI: 10.3390/md21050308.

Chemodiversity and Anti-Leukemia Effect of Metabolites from CMLD 18.

Calheiros de Carvalho A, Lima C, Torquato H, Domiciano A, da Cruz Silva S, de Abreu L Metabolites. 2023; 13(1).

PMID: 36676948 PMC: 9864219. DOI: 10.3390/metabo13010023.

A Metabolomics-Based Toolbox to Assess and Compare the Metabolic Potential of Unexplored, Difficult-to-Grow Bacteria.

Fiorini F, Bajerski F, Jeske O, Lepleux C, Overmann J, Bronstrup M Mar Drugs. 2022; 20(11).

PMID: 36421991 PMC: 9698959. DOI: 10.3390/md20110713.

Ion Mobility-Derived Collision Cross-Sections Add Extra Capability in Distinguishing Isomers and Compounds with Similar Retention Times: The Case of Aphidicolanes.

Xia J, Xiao W, Lin X, Zhou Y, Qiu P, Si H Mar Drugs. 2022; 20(9).

PMID: 36135730 PMC: 9503386. DOI: 10.3390/md20090541.

Novel Alkaloids from Marine Actinobacteria: Discovery and Characterization.

De Rop A, Rombaut J, Willems T, De Graeve M, Vanhaecke L, Hulpiau P Mar Drugs. 2022; 20(1).

PMID: 35049861 PMC: 8777666. DOI: 10.3390/md20010006.

References

McClure R, Goering A, Ju K, Baccile J, Schroeder F, Metcalf W . Elucidating the Rimosamide-Detoxin Natural Product Families and Their Biosynthesis Using Metabolite/Gene Cluster Correlations. ACS Chem Biol. 2016; 11(12):3452-3460. PMC: 5295535. DOI: 10.1021/acschembio.6b00779. View

Newman D, Cragg G . Natural Products as Sources of New Drugs over the Nearly Four Decades from 01/1981 to 09/2019. J Nat Prod. 2020; 83(3):770-803. DOI: 10.1021/acs.jnatprod.9b01285. View

Mohimani H, Pevzner P . Dereplication, sequencing and identification of peptidic natural products: from genome mining to peptidogenomics to spectral networks. Nat Prod Rep. 2015; 33(1):73-86. PMC: 5590107. DOI: 10.1039/c5np00050e. View

Schorn M, Verhoeven S, Ridder L, Huber F, Acharya D, Aksenov A . A community resource for paired genomic and metabolomic data mining. Nat Chem Biol. 2021; 17(4):363-368. PMC: 7987574. DOI: 10.1038/s41589-020-00724-z. View

Awakawa T, Crusemann M, Munguia J, Ziemert N, Nizet V, Fenical W . Salinipyrone and Pacificanone Are Biosynthetic By-products of the Rosamicin Polyketide Synthase. Chembiochem. 2015; 16(10):1443-7. PMC: 4545249. DOI: 10.1002/cbic.201500177. View

Mannle D, McKinnie S, Mantri S, Steinke K, Lu Z, Moore B . Comparative Genomics and Metabolomics in the Genus . mSystems. 2020; 5(3). PMC: 7413640. DOI: 10.1128/mSystems.00125-20. View

Cao L, Gurevich A, Alexander K, Naman C, Leao T, Glukhov E . MetaMiner: A Scalable Peptidogenomics Approach for Discovery of Ribosomal Peptide Natural Products with Blind Modifications from Microbial Communities. Cell Syst. 2019; 9(6):600-608.e4. PMC: 6952069. DOI: 10.1016/j.cels.2019.09.004. View

Hjorleifsson Eldjarn G, Ramsay A, van der Hooft J, Duncan K, Soldatou S, Rousu J . Ranking microbial metabolomic and genomic links in the NPLinker framework using complementary scoring functions. PLoS Comput Biol. 2021; 17(5):e1008920. PMC: 8130963. DOI: 10.1371/journal.pcbi.1008920. View

Wang M, Jarmusch A, Vargas F, Aksenov A, Gauglitz J, Weldon K . Mass spectrometry searches using MASST. Nat Biotechnol. 2020; 38(1):23-26. PMC: 7236533. DOI: 10.1038/s41587-019-0375-9. View

10.

Tong Y, Weber T, Lee S . CRISPR/Cas-based genome engineering in natural product discovery. Nat Prod Rep. 2018; 36(9):1262-1280. DOI: 10.1039/c8np00089a. View

11.

van der Hooft J, Wandy J, Young F, Padmanabhan S, Gerasimidis K, Burgess K . Unsupervised Discovery and Comparison of Structural Families Across Multiple Samples in Untargeted Metabolomics. Anal Chem. 2017; 89(14):7569-7577. PMC: 5524435. DOI: 10.1021/acs.analchem.7b01391. View

12.

Mohimani H, Kersten R, Liu W, Wang M, Purvine S, Wu S . Automated genome mining of ribosomal peptide natural products. ACS Chem Biol. 2014; 9(7):1545-51. PMC: 4215869. DOI: 10.1021/cb500199h. View

13.

Doroghazi J, Albright J, Goering A, Ju K, Haines R, Tchalukov K . A roadmap for natural product discovery based on large-scale genomics and metabolomics. Nat Chem Biol. 2014; 10(11):963-8. PMC: 4201863. DOI: 10.1038/nchembio.1659. View

14.

Kautsar S, Blin K, Shaw S, Navarro-Munoz J, Terlouw B, van der Hooft J . MIBiG 2.0: a repository for biosynthetic gene clusters of known function. Nucleic Acids Res. 2019; 48(D1):D454-D458. PMC: 7145714. DOI: 10.1093/nar/gkz882. View

15.

Nguyen D, Wu C, Moree W, Lamsa A, Medema M, Zhao X . MS/MS networking guided analysis of molecule and gene cluster families. Proc Natl Acad Sci U S A. 2013; 110(28):E2611-20. PMC: 3710860. DOI: 10.1073/pnas.1303471110. View

16.

Jarmusch A, Wang M, Aceves C, Advani R, Aguirre S, Aksenov A . ReDU: a framework to find and reanalyze public mass spectrometry data. Nat Methods. 2020; 17(9):901-904. PMC: 7968862. DOI: 10.1038/s41592-020-0916-7. View

17.

Navarro-Munoz J, Selem-Mojica N, Mullowney M, Kautsar S, Tryon J, Parkinson E . A computational framework to explore large-scale biosynthetic diversity. Nat Chem Biol. 2019; 16(1):60-68. PMC: 6917865. DOI: 10.1038/s41589-019-0400-9. View

18.

Aron A, Gentry E, McPhail K, Nothias L, Nothias-Esposito M, Bouslimani A . Reproducible molecular networking of untargeted mass spectrometry data using GNPS. Nat Protoc. 2020; 15(6):1954-1991. DOI: 10.1038/s41596-020-0317-5. View

19.

Asolkar R, Kirkland T, Jensen P, Fenical W . Arenimycin, an antibiotic effective against rifampin- and methicillin-resistant Staphylococcus aureus from the marine actinomycete Salinispora arenicola. J Antibiot (Tokyo). 2009; 63(1):37-9. PMC: 2825372. DOI: 10.1038/ja.2009.114. View

20.

Ernst M, Kang K, Caraballo-Rodriguez A, Nothias L, Wandy J, Chen C . MolNetEnhancer: Enhanced Molecular Networks by Integrating Metabolome Mining and Annotation Tools. Metabolites. 2019; 9(7). PMC: 6680503. DOI: 10.3390/metabo9070144. View