Use of microbiome technologies and bioassays for the search for new bioactive compounds in plants and symbionts: implications for metabolic responses, molecular diversity and bioactivity

• Grant number: 21/09693-5
• Support Opportunities: BIOTA-FAPESP Program - Regular Research Grants
• Start date: March 01, 2022
• End date: February 28, 2025
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Marcos José Salvador
• Grantee: Marcos José Salvador
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Candida Aparecida Leite Kassuya ; Derlene Attili de Angelis ; Fabiana Fantinatti Garboggini

Abstract

This research aims to carry out integrated investigations with plants (Amaranthaceae, Gesneriaceae and Annonaceae) and microorganisms from the microbiome of their leaf endosphere to evaluate the effect of plant/endophyte interactions on metabolic responses, molecular diversity and biosynthesis of bioactive substances. The main focus will be the search for substances with photoinduced biological effect for application in antimicrobial and antitumor PDT and/or protein Kinase C (PKC) inhibitors in plants and symbionts, using chemical and biological assays to direct the study. Therefore, the development of procedures for monitored study by bioassays will be sought, by analysis of absorption in the visible region of interest in PDT, evaluation of photochemical efficiency and by UHPLC-UV/DAD-ESI-MS, MS/ MS, NMR and the GNPS platform ("Global Natural Products Social Molecular Networking") in dereplication approaches. Plant species will be collected, identified and their extracts prepared, being then submitted to screening tests, being selected two plant species with better results in terms of chemical profile and bioactivity to continue the study. For the selected in natura plants, the aim will be to describe the diversity of microorganisms (bacteria and fungi) associated with the endosphere of their leaf blades and carry out the isolation and identification of cultivable microorganisms using culture media, microbiological analysis and molecular techniques. At first, for each of the plant species selected in the screening, a symbiotic microorganism with stable culture and higher biomass yield will be chosen to continue the integrated chemical, biological and biotechnological study. For the two plant species and microorganisms selected in the previous steps, we will seek to establish conditions for in vitro axenic cultivation and establish protocols for experimentation with pure cultures and synthetic co-cultures axenic/endophyte plant for proof of concept and for evaluating the effect of plant/endophyte interactions on plant metabolic responses, molecular diversity and bioactivity. Using genome mining tools, an analysis of the molecular genetics of the microorganisms selected in the study will be carried out to determine the biosynthetic gene clusters (BCG) of some of the identified molecules in order to explore the biosynthetic potential of endophytes. Promising extracts for bioactivity and with constituents that could not be identified in the dereplication step will be fractionated and, for active metabolites purified by the use of different chromatographic methods, their molecular structures will be determined using different methods analysis (IR, UV-vis, 1D and 2D NMR, mass spectrometry, specific rotation and circular dichroism). Therefore, with this study, investigations will be carried out in order to better understand the metabolic interactions between plant and its microbiota for prospecting (isolation and characterization) of bioactive molecules. This project also aims to train human resources (16 in guidance at the moment: 2PD, 9 Dr, 3 MS and 2 IC, all with CNPq, CAPES and FUNCAMP grants) able to carry out research of excellence for the generation of high-value technologies aggregate, combined with the conservation and sustainable use of biodiversity. (AU)

Scientific publications

(9)

(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)

WINIEWSKI, VANESSA; VERDAN, MARIA HELENA; OLIVEIRA, CRISTHIAN SANTOS; BARRETO RODRIGUES, TAYNA ELOYANE; SALVADOR, MARCOS JOSE; ALVES STEFANELLO, MARIA ELIDA. Two new naphthoquinone derivatives from Sinningia conspicua (Gesneriaceae). NATURAL PRODUCT RESEARCH, v. N/A, p. 6-pg., 2023-08-29. (12/09101-1, 06/06079-4, 21/09693-5, 15/03726-8)

OLIVEIRA, CRISTHIAN SANTOS; BARBOSA, FELIPE LUKACIEVICZ; EHRENFRIED, CARLOS AUGUSTO; RODRIGUES, TAYNA ELOYANE BARRETO; SALVADOR, MARCOS JOSE; ZAMPRONIO, ALEKSANDER ROBERTO; STEFANELLO, MARIA ELIDA ALVES. Chemical Constituents and Anti-inflammatory, Antinociceptive, and Antioxidant Activities of Salvia melissiflora Aerial Parts. REVISTA BRASILEIRA DE FARMACOGNOSIA-BRAZILIAN JOURNAL OF PHARMACOGNOSY, v. 34, n. 2, p. 8-pg., 2023-11-16. (09/05992-6, 15/03726-8, 21/09693-5, 06/06079-4)

SALUSTRIANO, FABRICIA RODRIGUES; DUENHAS MONREAL, ANTONIO CARLOS; DAS NEVES, SILVIA CORDEIRO; DE OLIVEIRA, GIOVANA MARTINS; MARQUES DE OLIVEIRA, DIEGO DUARTE; BRANDAO VILELA, MARCELO LUIZ; DO NASCIMENTO, VALTER ARAGAO; FAUSTINO MARTINS, ALLANA CRISTINA; SAROJA, BABY; KARUPPUSAMY, ARUNACHALAM; et al. The Ethanolic Extract of Gomphrena celosioides Mart. Does Not Alter Reproductive Performance or Embryo-Fetal Development, nor Does It Cause Chromosomal Damage. PHARMACEUTICS, v. 14, n. 11, p. 15-pg., 2022-11-01. (21/09693-5, 06/06079-4, 15/03726-8)

AGUERO ITO, CAREN NAOMI; SANTOS PROCOPIO, ELISANGELA DOS; BALSALOBRE, NATALIA DE MATOS; MACHADO, LUCAS LUIZ; SILVA-FILHO, SAULO EUCLIDES; PEDROSO, TAISE FONSECA; DE LOURENCO, CAROLINE CARAMANO; OLIVEIRA, RODRIGO JULIANO; ARENA, ARIELLE CRISTINA; SALVADOR, MARCOS JOSE; et al. Analgesic and Anti-Arthritic Potential of Methanolic Extract and Palmatine Obtained from Annona squamosa Leaves. PHARMACEUTICALS, v. 17, n. 10, p. 17-pg., 2024-10-01. (16/06407-3, 15/03726-8, 14/17436-9, 09/05992-6, 21/09693-5)

NEVES, SILVIA CORDEIRO DAS; NORONHA, RENATA COELHO RODRIGUES; MONREAL, ANTONIO CARLOS DUENHAS; DO NASCIMENTO, LUIS ADRIANO SANTOS; CARDOSO, ADAUTO LIMA; TAVARES, FLAVIA DOS SANTOS; TURA, BETHANIA BORGES; GOMES, ROBERTO DA SILVA; KASSUYA, CANDIDA APARECIDA LEITE; NUNES, VIKTOR KREJCI; et al. Absence of adverse effects of Blutaparon portulacoides (A.St.-Hil.) Mears in mice exposed during pregnancy. SOUTH AFRICAN JOURNAL OF BOTANY, v. 166, p. 8-pg., 2024-01-17. (15/03726-8, 06/06079-4, 21/09693-5)

REZENDE, GIOVANA CORBUCCI DANTI; NORONHA, RENATA COELHO RODRIGUES; ORTIZ, HUDMAN CUNHA; DO NASCIMENTO, LUIS ADRIANO SANTOS; DAS NEVES, SILVIA CORDEIRO; VENTURA SAID, YASMIN LANY; CARDOSO, ADAUTO LIMA; DE MESCOUTO, VANESSA ALBUQUERQUE; VILELA, MARCELO LUIZ BRANDAO; DO NASCIMENTO, VALTER ARAGAO; et al. Absence of maternal-fetal adverse effects of Alternanthera littoralis P. Beauv. following treatment during pregnancy in mice. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES, v. 86, n. 16, p. 14-pg., 2023-06-22. (06/06079-4, 21/09693-5, 15/03726-8)

HERNANDEZ-TASCO, ALVARO JOSE; TRONCHINI, RAFAELA APARECIDA; APAZA-CASTILLO, GLADYS ANGELICA; HOSAKA, GUILHERME KENICHI; QUINONES, NATALY RUIZ; GOULART, MARCELA CRISTINA; FANTINATTI-GARBOGGINI, FABIANA; SALVADOR, MARCOS JOSE. Diversity of bacterial and fungal endophytic communities presents in the leaf blades of Sinningia magnifica, Sinningia schiffneri and Sinningia speciosa from different cladus of Gesneriaceae family: A comparative analysis in three consecutive years. MICROBIOLOGICAL RESEARCH, v. 271, p. 10-pg., 2023-04-01. (21/09693-5, 15/03726-8, 17/03598-5, 06/06079-4, 12/09101-1)

TRAMONTINA, ROBSON; SCOPEL, EUPIDIO; CARDOSO, VICTOR GUSTAVO KELIS; MARTINS, MANOELA; DA SILVA, MARCOS FELLIPE; FLAIBAM, BARBARA; SALVADOR, MARCOS J.; GOLDBECK, ROSANA; DAMASIO, ANDRE; SQUINA, FABIO MARCIO. Hydroxycinnamic Acid Extraction from Multiple Lignocellulosic Sources: Correlations with Substrate Composition and Taxonomy for Flavoring and Antioxidant Applications. Journal of Agricultural and Food Chemistry, v. 72, n. 50, p. 12-pg., 2024-12-05. (20/02871-2, 22/08958-8, 19/19360-3, 21/04254-3, 22/05731-2, 21/09693-5, 15/50590-4)

MORAES, FERNANDA DOS SANTOS RAPUCCI; MORAES, LUIS HENRIQUE RAPUCCI; MACEDO, ALINE BARBOSA; VALDUGA, AMANDA HARDUIM; MIZOBUTI, DANIELA SAYURI; DA ROCHA, GUILHERME LUIZ; DA SILVA, HELOINA NATHALLIE MARIANO; SALVADOR, MARCOS JOSE; MINATEL, ELAINE. Anti-inflammatory and antioxidant activities of Citrus aurantifolia (Christm.) Swingle essential oil in dystrophic muscle cells: implication of the PGC-1α pathway. Journal of Essential Oil Bearing Plants, v. 27, n. 1, p. 13-pg., 2024-01-06. (12/09101-1, 21/09693-5, 17/01638-0, 10/01087-4, 13/17732-4, 06/06079-4, 15/03726-8, 11/02474-4, 20/09733-4)