Chemical Elicitors Induce Rare Bioactive Secondary Metabolites in Deep-Sea Bacteria under Laboratory Conditions
| Autor: | Sandra M. G. Dias, Luiz F. G. Alves, Gina Polo Infante, Fernanda Rodrigues-Costa, Renna Karoline Eloi Costa, Cristina Freitas Bazzano, Arthur Zanetti Nunes Fernandes, Luciana S. Paradela, Renata Sigrist, Guilherme P. Telles, André Oliveira de Souza Lima, Rafael de Felício, Marcus Adonai Castro da Silva, Luciane Alessandra Chimetto Tonon, Daniela B. B. Trivella, Patricia Ballone, Henrique Niero, Andréa Dessen |
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| Přispěvatelé: | Brazilian Biosciences National Laboratory (LNBio), National Center for Research in Energy and Materials, Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Institute of Computing [Campinas] (IC), Universidade Estadual de Campinas = University of Campinas (UNICAMP), School of Sea, Science and Technology, Universidade do Vale do Itajaí (UNIVALI), Institute of Computing [Campinas] (UNICAMP), Universidade Estadual de Campinas (UNICAMP) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Endocrinology Diabetes and Metabolism lcsh:QR1-502 Bacterial genome size 01 natural sciences Biochemistry lcsh:Microbiology Article drug discovery 03 medical and health sciences chemistry.chemical_compound Marine bacteriophage Molecular Biology bacterial natural products natural product libraries chemical elicitors cryptic gene clusters chemical space molecular networking dereplication deep-sea bacteria LC-MS/MS data mining Natural product biology [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry Molecular Biology/Structural Biology [q-bio.BM] 010405 organic chemistry Drug discovery Chemistry Biological activity biology.organism_classification Chemical space 0104 chemical sciences 030104 developmental biology Cheminformatics Bacteria |
| Zdroj: | Metabolites Metabolites, 2021, 11 (2), pp.107. ⟨10.3390/metabo11020107⟩ Metabolites, MDPI, 2021, 11 (2), pp.107. ⟨10.3390/metabo11020107⟩ Metabolites; Volume 11; Issue 2; Pages: 107 Metabolites, Vol 11, Iss 107, p 107 (2021) |
| ISSN: | 2218-1989 |
| DOI: | 10.3390/metabo11020107⟩ |
| Popis: | International audience; Bacterial genome sequencing has revealed a vast number of novel biosynthetic gene clusters (BGC) with potential to produce bioactive natural products. However, the biosynthesis of secondary metabolites by bacteria is often silenced under laboratory conditions, limiting the controlled expression of natural products. Here we describe an integrated methodology for the construction and screening of an elicited and pre-fractionated library of marine bacteria. In this pilot study, chemical elicitors were evaluated to mimic the natural environment and to induce the expression of cryptic BGCs in deep-sea bacteria. By integrating high-resolution untargeted metabolomics with cheminformatics analyses, it was possible to visualize, mine, identify and map the chemical and biological space of the elicited bacterial metabolites. The results show that elicited bacterial metabolites correspond to ~45% of the compounds produced under laboratory conditions. In addition, the elicited chemical space is novel (~70% of the elicited compounds) or concentrated in the chemical space of drugs. Fractionation of the crude extracts further evidenced minor compounds (~90% of the collection) and the detection of biological activity. This pilot work pinpoints strategies for constructing and evaluating chemically diverse bacterial natural product libraries towards the identification of novel bacterial metabolites in natural product-based drug discovery pipelines. |
| Databáze: | OpenAIRE |
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