Bioprospection in fungi: the search of lead compounds for drug design and enzymes for pharmaceutical and industrial applications

• Grant number: 04/07935-6
• Support type: BIOTA-FAPESP Program - Thematic Grants
• Duration: December 01, 2004 - November 30, 2008
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal researcher: Jairo Kenupp Bastos
• Grantee: Jairo Kenupp Bastos
• Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Pesquisadores principais: Maria de Lourdes Teixeira de Moraes Polizeli ; Mônica Tallarico Pupo ; SURAIA SAID
• Associated scholarship(s): 08/52732-7 - Biochemical characterization and spray drying of lipases produced by the endophytic fungus Cercospora kicuchii, BP.MS; 08/00812-7 - Evaluation of the biotechnological potential of endophytic actinobacteria isolated from Lychnophora ericoides ("falsa-arnica"), BP.DR; 08/01378-9 - Biontransformation of chlorogenic acid catalized by endophytic fungi, BP.IC; + associated scholarships 07/06057-3 - Mixed cultures as a strategy to improve endophytic fungi metabolite diversity, BP.MS; 06/50955-3 - Selection of soil fungi and lipase producing endophytics and adaptation of the cultivation conditions, BP.IC; 06/51604-0 - Bioprospection in fungi: the search of lead compounds for drug design and enzymes for pharmaceutical and industrial applications, BP.TT; 05/54133-5 - Bioprospection in filamentous fungi: study of alpha-amylase and glucoamylase in fungi isolated from the soil, decomposing matter and thermal waters, BP.DR; 05/51819-3 - Bioprospection in filamentous fungi: production and characterization of the pectinolytic complex, BP.MS; 05/58427-3 - Optimization of the cultivation conditions of endophytic VA 16 for production of secondary metabolites with biological activities , BP.MS; 05/58426-7 - Optimization of the cultivation conditions of endophytic fungus VA 27 for production of bioactive substances, BP.MS; 05/57116-4 - Optimization of the conditions of cultivating Humicola grisea var. Thermoidea, aimed at the production and isolation of biologically active secondary metabolites, BP.MS; 05/56999-0 - Study of the pectolytic system in filamentous fungi, BP.MS; 05/56259-6 - Search for endophylic microorganisms and their natural bioactive products in Smallanthus sonchifolius Poepp. & Endl. (Asteraceae), BP.PD; 05/55463-9 - Study of xilanases produced by filamentous fungi with potential for industrial application: selection of strains, production, biochemical charcaterization and phyolgenetic relationships, BP.DR; 05/56803-8 - Comparative study between the acidic and alkaline phosphatases produced by the Aspergillus niveus, Aspergillus niger and Aspergillus ochraceus fungi, BP.IC; 05/56411-2 - Evaluation of the antimicrobial activities of uncultivated extracts of cultures of 10 species of fungus isolated in the São Paulo Atlantic Rainforest, BP.IC; 05/54565-2 - Study of lipases produced by filamentous fungi, BP.IC - associated scholarships

Abstract

Fungi have been less explored than plants in bioprospection programs, especially the endophytes, which remain a promising and practically unexplored source of interesting bioactive natural products. One of the major advantages of working with microorganisms in a natural products discovery program is the possibility to screen a vast number of cultures on a small scale, before identifying the microorganisms, while retaining a high probability of success in reproducing both the activity and the metabolite production on a large-scale fermentation. Another advantage is that manipulations in culture conditions may lead to a wider range of compounds produced by fungi than it would be available from traditional production of extracts from plants. In this project we propose to exploit the chemical and biological potential of endophytic and soil fungi collected in São Paulo State in three approaches: i) obtainment of crude extracts from microbial cultures to be evaluated in antimicrobial assays performed in our labs and other bioassays provided by the network. The most promising extracts will be fractionated, aiming to obtain new leads for drug development; ii) obtainment of products from biotransformation reactions of bioactive natural products previously isolated in our labs (grandisin, budlein A and tagitinin C) and evaluation of their biological activities in bioassays of the network, and iii) production of enzymes, which might be useful in industrial processes (xylanase, glucose oxidase, phytase, amylase, acid and alkaline phosphatases) and as new pharmaceuticals (L-asparaginase). The proposed antimicrobial screening, as the first one, may be an indication of a wider ranger of bioactivity which shall be detected by the other assays available in the network. (AU)

Scientific publications

(18)

(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)

ANDRIOLI, W. J.; LOPES, A. A.; CAVALCANTI, B. C.; PESSOA, C.; NANAYAKKARA, N. P. D.; BASTOS, J. K. Isolation and characterization of 2-pyridone alkaloids and alloxazines from Beauveria bassiana. NATURAL PRODUCT RESEARCH, v. 31, n. 16, p. 1920-1929, 2017. Web of Science Citations: 1.

FRANCHI, L. P.; DE SOUZA, T. A. J.; ANDRIOLI, W. J.; LIMA, I. M. S.; BASTOS, J. K.; TAKAHASHI, C. S. The effects of the mycotoxin austdiol on cell cycle progression, cytotoxicity and genotoxicity in Chinese hamster ovary (CHO-K1) cells. WORLD MYCOTOXIN JOURNAL, v. 9, n. 2, p. 237-246, 2016. Web of Science Citations: 1.

COSTA-SILVA, T. A.; SOUZA, C. R. F.; OLIVEIRA, W. P.; SAID, S. CHARACTERIZATION AND SPRAY DRYING OF LIPASE PRODUCED BY THE ENDOPHYTIC FUNGUS Cercospora kikuchii. Brazilian Journal of Chemical Engineering, v. 31, n. 4, p. 849-858, OCT-DEC 2014. Web of Science Citations: 8.

ANDRIOLI, WILLIAN J.; CONTI, RAPHAEL; ARAUJO, MAGALI J.; ZANASI, RICCARDO; CAVALCANTI, BRUNO C.; MANFRIM, VIVIANE; TOLEDO, JULIANO S.; TEDESCO, DANIELE; DE MORAES, MANOEL O.; PESSOA, CLAUDIA; CRUZ, ANGELA K.; BERTUCCI, CARLO; SABINO, JOSE; NANAYAKKARA, DHAMMIKA N. P.; PUPO, MONICA T.; BASTOS, JAIRO K. Mycoleptones A-C and Polyketides from the Endophyte Mycoleptodiscus indicus. Journal of Natural Products, v. 77, n. 1, p. 70-78, JAN 2014. Web of Science Citations: 7.

ARAKAWA, NILTON SYOGO; GOBBO-NETO, LEONARDO; AMBROSIO, SERGIO RICARDO; ANTONUCCI, GILMARA AUSECH; SAMPAIO, SUELY VILELA; PUPO, MONICA TALLARICO; SAID, SURAIA; SCHMIDT, THOMAS J.; DA COSTA, FERNANDO BATISTA. Unusual biotransformation products of the sesquiterpene lactone budlein A by Aspergillus species. Phytochemistry, v. 96, p. 92-100, DEC 2013. Web of Science Citations: 10.

ROCHA, BRUNO ALVES; PUPO, MONICA TALLARICO; ANTONUCCI, GILMARA AUSECH; SAMPAIO, SUELY VILELA; ALVES PAIVA, RAQUEL DE MELO; SAID, SURAIA; GOBBO-NETO, LEONARDO; DA COSTA, FERNANDO BATISTA. Microbial transformation of the sesquiterpene lactone tagitinin C by the fungus Aspergillus terreus. Journal of Industrial Microbiology & Biotechnology, v. 39, n. 11, p. 1719-1724, NOV 2012. Web of Science Citations: 8.

ANDRIOLI, W. J.; SANTOS, M. S.; SILVA, V. B.; OLIVEIRA, R. B.; CHAGAS-PAULA, D. A.; JORGE, J. A.; FURTADO, N. A. J. C.; PUPO, M. T.; SILVA, C. H. T. P.; NAAL, R. M. Z. G.; BASTOS, J. K. delta-Lactam derivative from thermophilic soil fungus exhibits in vitro anti-allergic activity. NATURAL PRODUCT RESEARCH, v. 26, n. 23, p. 2168-2175, 2012. Web of Science Citations: 1.

COSTA-SILVA, TALES A.; NOGUEIRA, MARCO A.; FERNANDES SOUZA, CLAUDIA R.; OLIVEIRA, WANDERLEY P.; SAID, SURAIA. Lipase Production by Endophytic Fungus Cercospora kikuchii: Stability of Enzymatic Activity after Spray Drying in the Presence of Carbohydrates. Drying Technology, v. 29, n. 9, p. 1112-1119, 2011. Web of Science Citations: 17.

RAMOS, HENRIQUE PEREIRA; BRAUN, GLAUCIA HOLLANDER; PUPO, MONICA TALLARICO; SAID, SURAIA. Antimicrobial Activity from Endophytic Fungi Arthrinium state of Apiospora montagnei Sacc. and Papulaspora immersa. Brazilian Archives of Biology and Technology, v. 53, n. 3, p. 629-632, MAY-JUN 2010. Web of Science Citations: 14.

COSTA-SILVA, TALES A.; SAID, SURAIA; FERNANDES SOUZA, CLAUDIA R.; OLIVEIRA, WANDERLEY P. Stabilization of Endophytic Fungus Cercospora kikuchii Lipase by Spray Drying in the Presence of Maltodextrin and beta-Cyclodextrin. Drying Technology, v. 28, n. 11, p. 1245-1254, 2010. Web of Science Citations: 12.

COUTINHO GALLO, MARGARETH BORGES; CAVALCANTI, BRUNO COELHO; ARAUJO BARROS, FRANCISCO WASHINGTON; DE MORAES, MANOEL ODORICO; COSTA-LOTUFO, LETICIA VERAS; PESSOA, CLAUDIA; BASTOS, JAIRO KENUPP; PUPO, MONICA TALLARICO. Chemical Constituents of Papulaspora immersa, an Endophyte from Smallanthus sonchifolius (Asteraceae), and Their Cytotoxic Activity. CHEMISTRY & BIODIVERSITY, v. 7, n. 12, p. 2941-2950, 2010. Web of Science Citations: 14.

GALLO, MARGARETH B. C.; CHAGAS, FERNANDA O.; ALMEIDA, MARILIA O.; MACEDO, CLAUDIA C.; CAVALCANTI, BRUNO C.; BARROS, FRANCISCO W. A.; DE MORAES, MANOEL O.; COSTA-LOTUFO, LETICIA V.; PESSOA, CLAUDIA; BASTOS, JAIRO K.; PUPO, MONICA T. Endophytic fungi found in association with Smallanthus sonchifolius (Asteraceae) as resourceful producers of cytotoxic bioactive natural products. JOURNAL OF BASIC MICROBIOLOGY, v. 49, n. 2, p. 142-151, APR 2009. Web of Science Citations: 25.

GUIMARAES, DENISE O.; BORGES, KEYLLER B.; BONATO, PIERINA S.; PUPO, MONICA T. A Simple Method for the Quantitative Analysis of Tyrosol by HPLC in Liquid Czapek Cultures from Endophytic Fungi. Journal of the Brazilian Chemical Society, v. 20, n. 1, p. 188-194, 2009. Web of Science Citations: 6.

VERZA, MICHELLE; ARAKAWA, NILTON S.; LOPES, NORBERTO P.; KATO, MASSUO J.; PUPO, MONICA T.; SAID, SURAIA; CARVALHO, IVONE. Biotransformation of a Tetrahydrofuran Lignan by the Endophytic Fungus Phomopsis Sp.. Journal of the Brazilian Chemical Society, v. 20, n. 1, p. 195-U243, 2009. Web of Science Citations: 35.

LUCIANO DA S. MOMESSO; CRISTINA Y. KAWANO; PATRÍCIA H. RIBEIRO; AURO NOMIZO; GUSTAVO H. GOLDMAN; MÔNICA T. PUPO. Chaetoglobosinas produzidas por Chaetomium globosum, fungo endofítico associado a Viguiera robusta Gardn. (Asteraceae). Química Nova, v. 31, n. 7, p. -, 2008.

GUIMARÃES, DENISE O.; BORGES, WARLEY S.; KAWANO, CRISTINA Y.; RIBEIRO, PATRÍCIA H.; GOLDMAN, GUSTAVO H.; NOMIZO, AURO; THIEMANN, OTÁVIO H.; OLIVA, GLAUCIUS; LOPES, NORBERTO P.; PUPO, MONICA T. Biological activities from extracts of endophytic fungi isolated from Viguiera arenaria and Tithonia diversifolia. FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY, v. 52, n. 1, p. 134-144, 2008.

PUPO, MÔNICA TALLARICO; GALLO, MARGARETH BORGES COUTINHO; VIEIRA, PAULO CEZAR. Biologia química: uma estratégia moderna para a pesquisa em produtos naturais. Química Nova, v. 30, n. 6, p. 1446-1455, nov./dez. 2007.

BORGES, WARLEY DE SOUZA; PUPO, MÔNICA TALLARICO. Novel anthraquinone derivatives produced by Phoma sorghina, an endophyte found in association with the medicinal plant Tithonia diversifolia (Asteraceae). Journal of the Brazilian Chemical Society, v. 17, n. 5, p. 929-934, Sept./Oct. 2006.