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Cloning and functional characterization of oxidoesqualene cyclases of Maytenus ilicifolia

Grant number: 14/03819-3
Support type:Regular Research Grants
Duration: June 01, 2014 - May 31, 2016
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Cleslei Fernando Zanelli
Grantee:Cleslei Fernando Zanelli
Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Assoc. researchers:Maysa Furlan ; Tatiana Maria de Souza Moreira

Abstract

Among plant secondary metabolites, isoprenoids form a large and varied class of compounds with widely differing chemical structures and a variety of biological. Friedelin, a triterpene derived from isoprene, is found in the leaves of some plant species, such as Maytenus ilicifolia. This compound is itself biologically active and is also a precursor of the quinone methides tingenone and pristimerin, which are promising agents in the treatment of several cancer types, but they are produced only in the root bark of the young plant, which hampers its production. With the aim of characterizing the secondary metabolic pathways of those triterpenes and controlling their production, the terpene cyclases of a variety of plant species have been cloned. A strategy used frequently for the production of secondary metabolites is to employ genetically modified microorganisms. Such a strategy avoids predatory extraction and reduces the amounts of solvents required, making it an example of "green chemistry"; it also allows further genetic manipulation to improve the yield and opens the way to large-scale production. For these reasons, the objectives of this project are to clone the gene that encodes friedelin synthase of M. ilicifolia and to express it in Saccharomyces cerevisiae, genetically modified to improve the production of the triterpene in question. Thus, the project is designed to start by the identification of transcripts of oxidoesqualeno cyclases in the leaves of M. ilicifolia and going further with optimizing the protocols for cloning and expression of the M. ilicifolia oxidosqualene cyclase genes, then assessing the production of friedelin and other compounds by chromatographic methods, determining its specificity for the product friedelin and examining mutations that may result in better friedelin production profiles. (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)
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 MAR 2018. Web of Science Citations: 1.
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.; GUIDO, RAFAEL V. C.; FURLAN, MAYSA; ZANELLI, CLESLEI F. Friedelin Synthase from Maytenus ilicifolia: Leucine 482 Plays an Essential Role in the Production of the Most Rearranged Pentacyclic Triterpene. SCIENTIFIC REPORTS, v. 6, NOV 22 2016. Web of Science Citations: 8.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.