Bioprospecta program was created by FAPESP in order to support scientific research aiming prospection of terrestrial and marine organisms Submitted projects were peer reviewed and ranked according to quality, feasibility, coordinator and PIs CV, renewable resources and the sustainability approach. During the period 2010-2013, 11 projects were selected and being financed since.
BIOprospecTA
Pio Colepicolo, Ph.D. Departamento Bioquímica
Instituto de Química, USP
CURRENT PIPELINE OF ONGOING PROJECTS OF BIOPROSPECTA PROGRAM
11 projects under development
Summary of project features
BIOprospecTA
Standardized phytotherapics for the treatment of chronic diseases
Coordinator: Dr. Wagner Vilegas PI: Clélia Hiruma-Lima
Collaborators: 17 ICs (3 FAPESP), 10 MSc (3 FAPESP), 12 PhD (5 FAPESP), 9 PD (7 FAPESP)
Main objectives: - standardization of phytotherapics for the treatment of chronic diseases, according to Brazilian Pharmacopoeia.
Summary Results: - 20 plants were studied for assaying the activities - The chemical profile of the 20 extracts;
- Novel NPs were isolated from the stadardized extracts;
FAPESP # 2009/53237-9
Using metagenome as a tool to search new microbial natural products
Coordinator: Dr. Mônica Tallarico Pupo PIs: Denise Guimarães, Sean F Brady (Rockefeller University), Otavio H Thiemann,
Sérgio A Uyemura, Izaltina Cavalli Collaborators: 1 IC, 2 PhD (2 FAPESP)
Main objectives: - construction of metagenomic libraries of microorganisms from Atlantic Forest and Cerrado soil; - discovery of novel NP in these microorganisms. Summary results: • Biosynthesis of terpenoids • Six clones of microorganisms were identified as presenting anti-Leishmania activity
• Atlantic Forest Mevalonic Acid Pathway
• Cerrado Methylerythritol Phosphate Pathway
FAPESP # 2011/50869-8
Environmental stress and chemical and epigenetics modulation: strategies for exploring the metabolic and biological profile of endophytic fungi and marine cyanobacteria
Coordinator: Dr. Hosana M Debonsi
PIs: Marli F Fiore (CENA/USP), Nair S Yakoya (SMA/Ibt), Andre LM Porto (IQUSPSC), Sergio R
Ambrósio (UNIFRAN, SP), Niege AJC Furtado (FCFRP/USP), Lorena R Gaspar (FCFRP/USP), Fabíola A de Castro (FCFRP/USP), Lusânia MG Antunes (FCFPR/USP), Norberto P
Lopes (FCFRP/USP), Willian H Gerwick (Scripps Institution of Oceanography, UCSD, USA)
FAPESP # 2011/50836-2
Main objectives: - to bioprospect endophytic fungi and marine cyanobacteria for discovering novel NP; - epigenetic and genome sequencing studies of cultured cyanobacteria
submitted to a variety of putative elicitors.
Summary Results: - Up regulation (50% up) of jamaicamide in cyanobacteria; - Isolation o Carmaphycins from a cyanobacterium: proteassome inhibitors; - Isolation and identification of metabolites from marine endophytic fungi; - Isolation and identification of antibacterial compounds from seaweed;
Sustainable use of biodiversity from remaining areas of Atlantic Forest of São Paulo State – Evaluation, isolation and molecular characterization of bioactive secondary
metabolites from plants
Coordinator: Dr. João Henrique Ghilardi Lago PIs: Eliana Rodrigues (Unifesp, SP), Marcelo A Vallim (Unifesp, SP), Renata C Pascon (Unifesp, SP), Alisson L Matsuo (Unifesp, SP), Rafael C Guadagnin (Unifesp, SP), Carla Maximo Prado (Unifesp, SP), Alberto de Oliveira (UFU, MG), Marisi G Soares (UNIFAL, MG), André GT Cardoso (Instituto Adolfo Lutz – SP), Euder GA Martins (CEPEMA/USP – SP), Camilo Lellis-Santos (ICB-USP – SP), Abhay Satoskar - The Ohio State University (USA), Thomas Schmidt - Universität Münster (Germany), Gerold Jerz - TU Braunschweig (Germany), Marcelo Silva and Gabriela Santos-Gomes - Universidade Nova de Lisboa (Portugal) Collaborators: 4 ICs, 13 MSc, 2 PhD
Main objectives: - Isolation of active secondary metabolites of plants from Atlantic Forest.
Summary Results: - Set-up of bank of extracts from 75 plants; - Development of bioassay protocols for anti-inflammatory activity, anti-
tumoral, antiparasitic action, and antimicrobial; - About 25 NP compounds were isolated: some flavonoids, jacarone, pinenes,
triterpenoids, and alkaloids.
FAPESP # 2011/51739-0
Prospection of microbial metagenome from mangrove sediments in the search for novel bioactive compounds
Coordinator: Dr. Valeria Maia de Oliveira
PIs: Itamar S de Melo (Embrapa), Fernando Dini Andreote (ESALQ/USP), Anete Pereira de Souza (UNICAMP), Suzan P Vasconcellos (UNIFESP)
Collaborators: 1 MSc, 6 PhD, 3 PD
Main objectives: -prospection of bioactive compounds from microorganisms libraries isolated from polluted mangrove sediments.
Summary Results: - Isolation of bacterial strains producing enzymes involved with resistance the presence of pollutants: esterases, lipases, epoxide hydrolases, xylanases, chitinases, and dioxigenases.
FAPESP # 2011/50809-5
DESI-HTPLC –Bioautography: New strategies to rapid identification of anti-mastitis bioactive metabolites from actinomycetes
Coordinator: Dr. Luis A. Beraldo de Moraes
PIs: Tiago D. Zucchi, Marcos V. Santos, Ana Paula FP Izadora
Main objectives: - construction of actinomycetes library to support the prospection for novel NP presenting anti-mastitis activity.
Summary Results: - A series of NP were isolated from actinomycetes strains presenting activity anti-mastitis: actinomycins, nigericin, macrotetrolides, and valynomycin.
FAPESP # 2013/50729-7
Biotransformation of pimaradienoic acid (PA) by filamentous fungi and evaluation of the inhibitory effect on rat aorta contraction and on the Trypanossoma cruzi dihydroorotate dehydrogenase (DHODH) activity of the obtained derivatives
Coordinator: Dr. Sergio Ricardo Ambrosio
PIs: Hosana M Debonsi, Maria C Nonato, Niege AJC Furtado, Suraia Said Collaborations: 4 IC, 4 MSc, 2 PhD
Main objectives: - Biotransformation and bioprospection of Pimaradienoic Acid (PA) using filamentous fungi.
Summary Results: - Isolation of some NP derived from the transformation of PA, presenting
dihydroorotate dehydrogenase activity; - Isolation of some NP presenting anti-microbial and Schistosomidal activities
FAPESP # 2007/54762-8
Bioprospection of saprobe fungi from the Brazilian semi-arid northeast region for the control of infectious diseases in plants: induced resistance
Coordinator: Dr. Sergio F. Pascholati
PIs: Leonardo S Cavalcanti, Luis FP Gusmão, Júlio C Filho, Gaus S Lima, Fábio Augusto, Maria F Silva, Moacir R Forim, Francisco AO Tanaka, Luiz EA Camargo, Edson L Furtado,
Patrícia Cia, Eliane A Benato, Flávio HV Medeiros, Mário LV Resende, Fabrício A Rodrigues, Maria IB Penã, Marcelo Canteri, Kátia RF Schwan-Estrada, Jean Pierre Metraux, Wolfgang
Oswald, Holger B Deising, Karl-Heinz Kogel Collaborators: 48 IC, 25 MSc, 5 PhD, 11 PD
FAPESP # 2010/52343-0
Main objectives: - Construction of library of saprophytic fungi; - Isolation of NP with anti-infective action in plant
diseases for application in processes of biological control.
Summary Results: - 4 strain presenting inhibition of spore germination; - 12 strains presenting inhibition of mycelial growth; - 1 strain presenting reduction of sporulation; - 2 strains presenting inhibition of bacterial growth; - 7 strains with stimulatory activity of plant growth;
Bioprospection of yeasts and filamentous fungi from different biomes of the State of São Paulo in order to produce enzymes, vitamins and bioactive compounds of industrial interest
Coordenadora: Dr. Gabriela Alves Macedo
Collaborators: 2 MSc, 1 PhD
Main objectives: - Search of yeasts and fungi strains producing enzymes, vitamins, and antibiotics, for industrial applications.
Summary Results: - Yeasts prospection * 13 strains presenting lipase activity; * 4 strains producing biotin; * 15 strain producing riboflavin; - Filamentous fungi prospection * 9 strain presenting lipase activity; * 18 strains presenting tanase activity; * 22 strains presenting anti-microbial activity.
FAPESP # 2011/50881-8
Development of a platform to study the in vivo and in vitro metabolism of NP: a demand for pre-clinical assays
Coordinator: Prof. Dr. Norberto Peporini Lopes
PIs: Mônica T Pupo, Alberto J Cavalheiro, Anderson RM de Oliveira, Flavio S Emery, Giuliano Clososki, Hans Humpft, João LC Lopes, José NC Lopes, Marilda D Assis, Massuo J
Kato, Niege AJC Furtado, Ricardo Vessecchi, Sérgio E Galembeck, Thais Guaratini, Valquíria Jabor, Vanderlan S Bolzani
FAPESP # 2009/51812-0
Main objectives: - Study of the metabolism of NP in pre-clinical assays.
Summary Results: - Development of a complex experimental platform for in vivo and in vitro studies of NP based on bioassays and spectroscopy; - 40 NP compounds were initially studied to test all the platform; 4
compounds achieved the PK studies; - The complete work-flow of the platform is ready to be used in the pre-clinical
assays of novel NP;
Prospection of bioactive molecules and study of infra-specific variability in plants and endophytic microorganisms from Cerrado and Caatinga: a contribution for the knowledge
and sustainable use of Brazilian biodiversity
Coordinator: Dra. Vanderlan Bolzani PIs: Alberto J Cavalheiro, Roseli B Torres, Antonio AJ Farias, Maria GL Brandão, Ian C
Gamboa, Dulce HS Silva, Angela R Araújo, Maria GV Silva, Marcia Graminha
Main Objectives: • Access and documentation of vegetal diversity • Prospection of bioactive substances • Genetic variability and infra-specific chemistry • Construction of libraries of microorganisms isolated from cerrado
and caatinga; • Isolation and structural characterization of bioactive NPs from
microorganism extracts
FAPESP # 2010/52327-5
Summary Results: • Recovery the historic informations about vegetal diversity of Cerrado and Caatinga; • Set-up experimental workflow of NP prospection based on biological activities
assaying, genomics, purification strategies, structural elucidations, (bio)synthesis of novel NP discovered and some analogs for developments of medicines and cosmetics;
• Development and implementation of a DB about phytochemistry and MedChem - The NuBBE DB.
• A series of sesquiterpenes presenting anti-Leishmaniasis and anti-protozoal activity were isolated and structurally characterized.
System Biology as Experimental Strategy for the Discovery of Novel NP in the Fauna of Arthropods of São Paulo State
Coordinator: Dr. Mario S. Palma
PIs: João Ruggiero Neto, Flavio de Oliveira Lima, Lucilene D Santos Collaborators: 4 IC, 2 MSc, 3 PhD
Main objectives: - prospection of a series of secretions of venomous Arthropods using metabolomics, peptidomics, and proteomics as experimental approaches, in the search for novel bioactive NP
FAPESP # 2011/51684-1
Summary Results: - Many low molecular mass (LMM) toxins were purifed and structurally
elucidated from the venom of wasps and spiders: acylpolyamines, tetrahydro--carbolines, and histaminylglucosides;
- Amongst the LMM toxins isolated two of them presented potent anti-epileptic actions, both in vitro and in vivo assay models;
- Peptidomic studies revealed some anti-inflammatory peptides isolated from wasps venom, which play their actions through an unusual inhibition of COX2, by blocking the access of oxygen to the heme group, preventing the peroxydation of the substrate (arachdonic acid).
Biotechnological and metabolic potential of marine organisms for bioremediation processes and production of substance with antiviral, anti-inflammatory , and
anti-Leishmania activity
Coordinator: Dr. Roberto Gomes de Souza Berlinck PIs: Lara D Sette (IB-UNESP-Rio Claro), Clarice W Arns (IB-UNICAMP), André G Tempone
(Inst. Adolfo Lutz), Alexandra I Medeiros (FCF-UNESP-Araraquara), David H Sherman (University of Michigan)
FAPESP # 2010/51190-2
Main objectives: - Bioprospection of compounds presenting anti-inflammatory, anti-viral, and
anti-Leishmania activities, isolated from marine organisms.
Arenosclera brasieliensis
Summary Results: - Construction of a library of marine microorganisms; - isolation of series of metabolites from macro- and microorganisms; - 3 strains of basidiomycetes were isolated from marine sponges, with good potential to be used in bioremediation processes. - Microbiome and metagenome of sponges
Marine macroalga cultivated in polluted areas and application of their metabolites with economical impact
Coordinator: Pio Colepicolo
PIs: Drs. Ernani Pinto (FCF-USP), Norberto P. Lopes (FCFRP-USP), Nair S Yokoya (IBt/SMA), Mutue T Fuji (IBt/SMA), Marcia Mesko (UFPel), Eliane Marinho-Soriano (UFRN), Marcia Graminha (FCF-UNESP) and
Paulo Horta (UFSC)
FAPESP # 2010/51293-1
Objective: Study the biodiversity of tropical macroalgae and isolate important compounds with food, pharmaceutical, cosmetic and bioenergy applications.
SUMMARY OF RESULTS
1. Harvesting, biodiversity and lab cultivation
2. Photosynthetic rates
3. Development of analytical platforms using LCMS/MS and CGMS
4. Isolation of metabolites with economical impact and application
• carotenoids
• polysaccharides
• lipids, including w-3 and w-6 families
• Mycosporine-Like Amino Acids (MAA) and cytotoxicity / phototoxicity assays
SUMMARY OF RESULTS
Crop harvest; 3 months latter
5. Chemical elucidation of new metabolites
6. Metal toxicity effects on the redox potential
lipid, DNA and protein damage
analysis of glutathione and GSSG
induction of phytochelatin
proteomic, transcriptomic and metabolomic analysis
7. Biological activities, such as antioxidant,
bactericide, fungicide, anticancer and
leishmanicidal (Dr. M. Graminha; FCF-UNESP)
8. Sustainable cultivation of macroalgae
at seashore and joint cultivation in order to obtain
large amount of algae biomass
Structure of Glutathione
IN SUMMARY, Biological Activities Under Investigation:
• Anti-Leishmania * Anti-Epiletic
• Anti-Oxidant * Inhibition of Plant Sporulation
• Anti-Viral * Inhibition of Plant Growth
• Anti-Microbial * Anti-Inflammatory
• Anti-Schistosomosis * Anti-Cancer
• Anti-Ulcer * Anti-Tumoral
Enzyme Activities Under Investigation:
• Esterases * Lipases
• Epoxide hydrolases * Xylanases
• Chitinases * Tanase
• Antioxidant enzymes
• Topoisomerases
• Celulases
BIOprospecTA
Processes:
• Fermentation
• Fuel production
• Biofilm production
• Environmental Bioremediation
…in numbers (2011-2014)
BIOprospecTA
Products Production of the Program
Scientific Publications in Indexed Journals 438
Citations 1581
Human Resources (Ph.D. Thesis and Master Dissertations presented)
159
Book Chapters 8
Books 3
Knowledge Dissemination 53
Oral Presentations 194
Patents 9
Web of Science (Nov. 15th)
Prepared by: Mario Palma and Pio Colepicolo under coordination of Roberto Berlinck
BIOprospecTA