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Obtaining a compound with cytotoxic activity by Streptomyces SP. - development of production, analysis and purification protocols

Grant number: 13/00539-7
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): September 01, 2013
Effective date (End): August 31, 2015
Field of knowledge:Engineering - Chemical Engineering - Chemical Process Industries
Principal Investigator:Alberto Colli Badino Junior
Grantee:Liliane Maciel de Oliveira
Home Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

Gymnangiamida is a pentapeptide firstly isolated from a marine hydroid which showed cytotoxic activity against some cancer cell lines. After its discovery in 2004, just one paper reporting the chemical synthesis of this compound was published in the literature, in 2009. Recent studies have been started in the departments of Chemical Engineering (DEQ) and Chemistry (DQ), at Federal University of São Carlos (UFSCar), and led to the isolation of a gymnangiamide isomer from the culture broth of a marine strain of Streptomyces sp. The butanolic fraction in which the compound was isolated also showed cytotoxic activity against brain and colon's tumor cells. This discovery led to the development of the present research project, which aims to develop protocols of production, analysis and purification of this compound by the marine strain of Streptomyces sp., in order to obtain sufficient quantities that enables the continuity of the preclinical trials - toxicity assays and in vitro (cells) and in vivo (animal) activity assays. To achieve the final purpose, the following steps are proposed: development of an analytical methodology for quantification of the compound in the culture broth; evaluation of different culture media for gymnangiamide production; assessment of the fed-batch fermentation for increase of gymnangiamide production; process validation by fermentations carried out in bioreactors. In the purification studies, it is proposed here the use of microfiltration and ultrafiltration of the culture broth; evaluation of different organic solvents to extract the compound from the ultrafiltered broth; and development of a liquid chromatography methodology in semi-preparative scale to obtain the pure compound. The results of this project will allow the continuation of the gymnangiamide's cytotoxic activity studies, with a view to future use of the compound as a drug. Furthermore, the production and purification protocols developed may be used as the basis for future studies in obtaining an analytical standard of the compound.