Integrated strategies for natural product discovery from Brazilian cyanobacteria

• Grant number: 22/02872-4
• Support Opportunities: Research Grants - Initial Project
• Start date: April 01, 2023
• End date: March 31, 2028
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Camila Manoel Crnkovic
• Grantee: Camila Manoel Crnkovic
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Alessandra S Eustaquio ; Frederico José Gueiros Filho ; Leticia Veras Costa Lotufo ; Roger Linington
• Associated scholarship(s): 25/02439-7 - Sequencing and mining Brazilian cyanobacterial genomes to identify biosynthetic gene clusters, BP.IC; 25/03645-0 - Metabolomics for dereplicating natural products from cyanobacteria, BP.MS; 24/00339-2 - Communicating Science: From Biodiversity to Natural Products Biotechnology, BP.JC; + associated scholarships 24/00342-3 - Communicating Science: From Biodiversity to Natural Products Biotechnology, BP.JC; 24/04602-0 - Building a chemical library of prefractionated extracts from cyanobacteria, BP.TT; 24/02692-1 - Microscale dereplication to expedite the discovery of natural products from cyanobacteria, BP.DD; 23/05381-4 - Building a chemical library of prefractionated extracts from cyanobacteria, BP.TT; 23/03532-5 - Exploring elicitor screening for prospecting natural products from cyanobacteria, BP.IC - associated scholarships

Abstract

Natural products continue to provide important chemical scaffolds for the development of pharmaceutical drugs. Prospecting understudied organisms and utilizing orthogonal approaches are strategies that can be integrated to improve natural product discovery. Cyanobacteria are photosynthetic prokaryotes known to produce secondary metabolites with biological activity. Nonetheless, the chemistry of cyanobacteria remains understudied. Our research group has implemented a pipeline for creating a library of prefractionated extracts from cultured cyanobacteria. Biological assays along with metabolomics have been employed for analyzing and prioritizing samples for follow up investigations. In this project, we propose to extend this pipeline towards systematizing dereplication and achieving the isolation and elucidation of novel natural products from Brazilian cyanobacteria. We will also diversify prospection approaches aiming at augmenting the chances of discovery. Prefractionated extracts will be subjected to a secondary HPLC fractionation followed by microscale dereplication using mass spectrometry and nuclear magnetic resonance spectroscopy. An additional dereplication strategy will combine stable isotope labeling and metabolomics. Complementary prospection strategies based on genome mining and elicitor screening will be applied. Novel and bioactive molecules will be prioritized for isolation and structure elucidation. This project aims at establishing a line of research in microbial natural product discovery at the School of Pharmaceutical Sciences (USP). It will create research opportunities for undergraduate, masters, and Ph.D. students. We also propose to update the scope of a graduate-level course and an undergraduate course, as well as to develop a collaborative textbook addressing topics related to the current project. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ALMEIDA, ERYKA COSTA; JACINAVICIUS, FERNANDA RIOS; PASSOS, LARISSA SOUZA; MEDICE, RHUANA VALDETARIO; MARQUES, LUCAS GREGORIO; CRNKOVIC, CAMILA MANOEL; MARINHO, MARCELO MANZI; GOMES, LEVY DE CARVALHO; PINTO, ERNANI. Phytoplankton composition and metabolomic profiles in aquaculture systems: A case study in Brazil's natural lakes. Aquaculture, v. 599, p. 13-pg., 2025-01-17. (22/02872-4, 21/14239-1, 24/02448-3, 13/07914-8, 21/00149-0)

CAMPOS, THAISSA GIOVANNA VALVERDE; GAMA, WATSON A.; GERALDES, VANESSA; YOON, JAEWON; CRNKOVIC, CAMILA M.; PINTO, ERNANI; JACINAVICIUS, FERNANDA RIOS. New records on toxic cyanobacteria from Brazil: Exploring their occurrence and geography. Science of The Total Environment, v. 931, p. 14-pg., 2024-05-03. (22/02872-4, 24/02448-3, 21/10573-4, 20/07710-7, 19/27707-3, 23/00525-8, 13/07914-8, 21/00149-0)

WEISS, MARCIO B.; BORGES, RICARDO M.; SULLIVAN, PETER; DOMINGUES, JOAO P. B.; DA SILVA, FRANCISCO H. S.; TRINDADE, VICTORIA G. S.; LUO, SHANGWEN; ORJALA, JIMMY; CRNKOVIC, CAMILA M.. Chemical diversity of cyanobacterial natural products. NATURAL PRODUCT REPORTS, v. N/A, p. 44-pg., 2024-11-14. (22/02872-4, 19/17721-9, 21/14754-3, 20/07710-7)