Chemical Elicitors Induce Rare Bioactive Secondary Metabolites in Deep-Sea Bacteria under Laboratory Conditions

Autor(es):Mostrar menos -

de Felicio, Rafael ^[1] ; Ballone, Patricia ^{[2, 1]} ; Bazzano, Cristina Freitas ^{[1, 3]} ; Alves, Luiz F. G. ^[1] ; Sigrist, Renata ^[1] ; Infante, Gina Polo ^[1] ; Niero, Henrique ^{[2, 1]} ; Rodrigues-Costa, Fernanda ^{[2, 1]} ; Fernandes, Arthur Zanetti Nunes ^{[2, 1]} ; Tonon, Luciane A. C. ^[1] ; Paradela, Luciana S. ^[1] ; Costa, Renna Karoline Eloi ^[1] ; Dias, Sandra Martha Gomes ^[1] ; Dessen, Andrea ^{[1, 4]} ; Telles, Guilherme P. ^[3] ; da Silva, Marcus Adonai Castro ^[5] ; Lima, Andre Oliveira de Souza ^[5] ; Trivella, Daniela Barretto Barbosa ^[1]

Afiliação do(s) autor(es)

^[1] Natl Ctr Res Energy & Mat CNPEM, Brazilian Biosci Natl Lab LNBio, BR-13083970 Campinas, SP - Brazil

^[2] Univ Campinas UNICAMP, Inst Biol, BR-13083862 Campinas, SP - Brazil

^[3] Univ Campinas UNICAMP, Inst Comp IC, BR-13083852 Campinas, SP - Brazil

^[4] Univ Grenoble Alpes, CNRS, Inst Biol Struct IBS, CEA, F-38000 Grenoble - France

^[5] Univ Vale Itajai Univali, Sch Sea Sci & Technol, BR-88302202 Itajai, SC - Brazil

• Tipo de documento: Artigo Científico
• Fonte: METABOLITES; v. 11, n. 2 FEB 2021.
• Citações Web of Science: 0

Resumo

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 similar to 45% of the compounds produced under laboratory conditions. In addition, the elicited chemical space is novel (similar to 70% of the elicited compounds) or concentrated in the chemical space of drugs. Fractionation of the crude extracts further evidenced minor compounds (similar to 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. (AU)

• Processo FAPESP: 14/10753-9 - Bioprospecção e desenho racional para a descoberta de novas gerações de inibidores do proteassomo
• Beneficiário: Daniela Barretto Barbosa Trivella
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/12436-9 - ANTIBIO-BAC: a parede bacteriana como alvo para o desenvolvimento de novos agentes antimicrobianos
• Beneficiário: Andrea Dessen de Souza e Silva
• Modalidade de apoio: Auxílio à Pesquisa - Programa SPEC
• Processo FAPESP: 15/19906-5 - Identificação de novos agentes anti-bacterianos em bibliotecas de produtos naturais
• Beneficiário: Fernanda Rodrigues da Costa
• Modalidade de apoio: Bolsas no Brasil - Doutorado