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Study of the triterpene transporters in the Saccharomyces cerevisiae model

Grant number: 17/01193-8
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): April 01, 2017
Effective date (End): March 31, 2019
Field of knowledge:Physical Sciences and Mathematics - Chemistry
Principal Investigator:Maysa Furlan
Grantee:Bianca Rodrigues
Home Institution: Instituto de Química (IQ). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Secondary metabolites are produced by plants to perform protective functions, such as insecticides, antimicrobials and photoprotectors However, it was noted that some of these metabolites present therapeutic activity, such as morphine, obtained from Papaver somniferum, which was one of the first anesthetics discovered and it is still widely used. Among these metabolites, are highlighted the triterpenes like friedelanol and friedelin found in Maytenus ilicifolia species, popularly known as "espinheira santa". Friedelin is the main responsible for the gastroprotective and anti-inflammatory activity of "espinheira santa", and it is metabolized to the quinonemethides maytenin and pristimerin, by action of the oxidorredutases enzymes. These quinonemethides are mainly found in the barks of the roots of Maytenus ilicifolia, maytenin is in greater amount and presents antineoplastic activity, while pristimerin presents antioxidant, antimicrobial, antineoplastic and anti-inflammatory activity, being then potential agents of therapeutic use. However, this future therapeutic activity would be unviable if the production process of these compounds is not amplified, since industrial quantities will be required. For this, the present project proposes a tracking of the possible transporters of these substances in Saccharomyces cerevisiae, that can be a potential large scale producer due to the presence of all the necessary genetic machinery together with techniques of Synthetic Biology. The knowledge of these transporters allows the optimization of the process by overexpressing efflux pumps that will promote the exit of these newly produced compounds and avoid the toxicity that they present when in excess in the intracellular medium. In addition, it is also possible to subexpress the carriers responsible for the entry of these substances into the extracellular medium, which would imply toxicity. (AU)