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Grant number: 11/10379-1
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): September 01, 2011
Effective date (End): August 31, 2016
Field of knowledge:Health Sciences - Pharmacy
Principal Investigator:Maysa Furlan
Grantee:Tatiana Maria de Souza Moreira
Host Institution: Instituto de Química (IQ). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Associated research grant:13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery, AP.CEPID
Associated scholarship(s):14/25705-0 - Metabolic engineering of the ergosterol pathway of Saccharomyces cerevisiae to improve production of the triterpene friedelin, BE.EP.PD


Isoprenes are one of the classes of plant secondary metabolites with different chemical structures and several biological and therapeutic activities. Friedelin is a triterpene derivate found in the leaves of some species such as Maytenus ilicifolia that shows biological activities and is precursor of the triterpene quinonemethides maytenin and pristimerin. They are important marker molecules for the species and they are present in phytotherapics used in the treatment of gastric disorders. However, they are just produced in the root bark of young plants. Different biosynthetic pathways give as result from the oxidosqualene molecule membrane sterois of plant, fungus and animal, plant and animal hormones or plant secondary terpenes. Several vegetal species had their terpene cyclases from secondary metabolism cloned in order to characterize the secondary terpene derivate pathways and to control their production. One of the most important options to produce secondary metabolites is the utilization of genetically modified microorganisms. The use of those microorganisms avoids the predatory harvesting, uses less solvents and therefore is a "green chemistry" practice. Microorganisms constitute a faster renewable source of metabolites than plants, utilize cheaper carbon sources, allow genetic manipulation for increasing the yield of production and make possible the production in large scale. Thus, the objectives of this project are cloning the friedelin synthase gene from the leaves of M. ilicifolia and expressing it in genetically modified Saccharomyces cerevisiae to improve the production of friedelin. The project is organized to be developed in two years, beginning by the standardization of PCRs for cloning and expression protocols of oxidosqualene cyclase from M. ilicifolia, evaluating production of friedelin and other compounds by chromatographic methods, identifying the phylogenetic aspects of the cloned enzyme, specificity for the product friedelin and mutations that can result in better profiles of friedelin production.

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Scientific publications (4)
(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)
F. COTINGUIBA; H. M. DEBONSI; R. V. SILVA; R. M. PIOLI; R. A. PINTO; L. G. FELIPPE; S. N. LÓPEZ; M. J. KATO; M. FURLAN. Participação dos aminoácidos L-fenilalanina e L-lisina na biossíntese de piperamidas trans e cis em duas espécies de Piper. Brazilian Journal of Biology, v. 82, . (11/10379-1, 14/25705-0, 14/03819-3, 06/50086-5)
SOUZA-MOREIRA, TATIANA M.; ALVES, THAS B.; PINHEIRO, KARINA A.; FELIPPE, LIDIANE G.; DE LIMA, GUSTAVO M. A.; WATANABE, TATIANA F.; BARBOSA, CRISTINA C.; SANTOS, VANIA A. F. F. M.; LOPES, NORBERTO P.; VALENTINI, SANDRO R.; et al. Friedelin Synthase from Maytenus ilicifolia: Leucine 482 Plays an Essential Role in the Production of the Most Rearranged Pentacyclic Triterpene. SCIENTIFIC REPORTS, v. 6, . (12/21005-8, 13/07600-3, 13/15306-8, 14/03819-3, 11/10379-1, 12/09584-2)
ALVES, THAIS B.; SOUZA-MOREIRA, TATIANA M.; VALENTINI, SANDRO R.; ZANELLI, CLESLEI E.; FURLAN, MAYSA. Friedelin in Maytenus ilicifolia Is Produced by Friedelin Synthase Isoforms. Molecules, v. 23, n. 3, . (14/03819-3, 13/07600-3, 11/10379-1)
MAZZEU, BRUNA F.; SOUZA-MOREIRA, TATIANA M.; OLIVEIRA, ANDREW A.; REMLINGER, MELISSA; FELIPPE, LIDIANE G.; VALENTINI, SANDRO R.; GUIDO, RAFAEL V. C.; ZANELLI, CLESLEI F.; FURLAN, MAYSA. The Methionine 549 and Leucine 552 Residues of Friedelin Synthase from Maytenus ilicifolia Are Important for Substrate Binding Specificity. Molecules, v. 26, n. 22, . (13/07600-3, 11/10379-1, 14/25705-0, 14/50926-0)

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