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

Author(s):Show less -

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]

Affiliation

^[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

• Document type: Journal article
• Source: METABOLITES; v. 11, n. 2 FEB 2021.
• Web of Science Citations: 0

Abstract

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)

• 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: 17/12436-9 - ANTIBIO-BAC: exploring the bacterial cell wall as a target for novel antibiotherapies
• Grantee: Andrea Dessen de Souza e Silva
• Support Opportunities: Research Projects - SPEC Program
• FAPESP's process: 15/19906-5 - Identification of new antibacterial agents in libraries of natural products
• Grantee: Fernanda Rodrigues da Costa
• Support Opportunities: Scholarships in Brazil - Doctorate