NP³ MS Workflow: An Open-Source Software System to Empower Natural Product-Based Drug Discovery Using Untargeted Metabolomics

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Bazzano, Cristina F. ; de Felicio, Rafael ; Alves, Luiz Fernando Giolo ; Costa, Jonas Henrique ; Ortega, Raquel ; Vieira, Bruna Domingues ; Morais-Urano, Raquel Peres ; Furtado, Luciana Costa ; Ferreira, Everton L. F. ; Gubiani, Juliana R. ; Berlinck, Roberto G. S. ; Costa-Lotufo, Leticia V. ; Telles, Guilherme P. ; Trivella, Daniela B. B.

• Document type: Journal article
• Source: Analytical Chemistry; v. 96, n. 19, p. 10-pg., 2024-05-03.

Abstract

Natural products (or specialized metabolites) are historically the main source of new drugs. However, the current drug discovery pipelines require miniaturization and speeds that are incompatible with traditional natural product research methods, especially in the early stages of the research. This article introduces the NP3 MS Workflow, a robust open-source software system for liquid chromatography-tandem mass spectrometry (LC-MS/MS) untargeted metabolomic data processing and analysis, designed to rank bioactive natural products directly from complex mixtures of compounds, such as bioactive biota samples. NP3 MS Workflow allows minimal user intervention as well as customization of each step of LC-MS/MS data processing, with diagnostic statistics to allow interpretation and optimization of LC-MS/MS data processing by the user. NP3 MS Workflow adds improved computing of the MS2 spectra in an LC-MS/MS data set and provides tools for automatic [M + H](+) ion deconvolution using fragmentation rules; chemical structural annotation against MS2 databases; and relative quantification of the precursor ions for bioactivity correlation scoring. The software will be presented with case studies and comparisons with equivalent tools currently available. NP3 MS Workflow shows a robust and useful approach to select bioactive natural products from complex mixtures, improving the set of tools available for untargeted metabolomics. It can be easily integrated into natural product-based drug-discovery pipelines and to other fields of research at the interface of chemistry and biology. (AU)

• FAPESP's process: 15/01017-0 - Multi-use instrument approved and awarded in the project 2013/50228-8, name of instrument: ultra-performance liquid chromatograph coupled with a high resolution mass spectrometer
• Grantee: Roberto Gomes de Souza Berlinck
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 19/17721-9 - The role of Chemistry in holobiont adaptation
• Grantee: Roberto Gomes de Souza Berlinck
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/50228-8 - Biodiversity components, and their metabolic characters, of Brazilian Islands: an integrated approach
• Grantee: Roberto Gomes de Souza Berlinck
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants
• FAPESP's process: 14/10753-9 - Bioprospecting and rational design for the discovery of next generation proteasome inhibitors
• Grantee: Daniela Barretto Barbosa Trivella
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/17177-6 - Integrative approach on the sustainable prospection of marine natural products: from diversity to anticancer compounds
• Grantee: Leticia Veras Costa Lotufo
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants
• FAPESP's process: 17/18235-5 - Anticancer potential of isolated substances from Streptomyces SP. recovered from ascidian Euherdmania SP
• Grantee: Luciana Costa Furtado
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 20/08987-2 - Effect of histone deacetylase and proteasome inhibitors in Glioma models
• Grantee: Luciana Costa Furtado
• Support Opportunities: Scholarships in Brazil - Doctorate