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Doctoral Thesis
DOI
https://doi.org/10.11606/T.87.2007.tde-17042008-092436
Document
Author
Full name
Charlotte Cesty Borda de Saenz
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2007
Supervisor
Committee
Maldonado, Gabriel Padilla (President)
Araujo, Welington Luiz de
Gomez, José Gregorio Cabrera
Severino, Patrícia
Torres, Bayardo Baptista
Title in Portuguese
Estudos de genes envolvidos na via biossintética do antibiótico antitumoral Cosmomicina
Keywords in Portuguese
antibióticos
biblioteca genômica
genes reguladores
glicosiltransferases
policetídeos
Streptomyces olindensis
Abstract in Portuguese
Cosmomicina é um antibiótico antitumoral produzido pela bactéria Streptomyces olindensis DAUFPE 5622. Estudos de expressão gênica demonstraram que genes cuja expressão esta relacionada a condições de estresse (dnaJ e 18hsp), assim como genes associados a via biossintética de cosmomicina, são expressos sob condições de produção do antibiótico. Genes que ainda tinham a função desconhecida foram selecionados (cosS e cosY) e foram realizados análises bioinformáticas destes atribuindo-lhes a função de regulador transcricional e ornitina ciclodesaminase, respectivamente. Um cassete para inativação desses genes foi construído visando a futura obtenção de mutantes nulos. Genes de glicosiltransferase (cosK e cosG) também apresentaram diferenças na expressão na presença do antibiótico. Neste trabalho, foi revelada a presença de uma hipotética glicosiltransferase que tem homologia com a B-daunosamine daunomy, glicosiltransferase envolvida na transferência de açúcares na biossíntese do antibiótico daunomicina.
Title in English
Genes study envolved in biosynthetic pathway of antitumoral antibiotic Cosmomycin.
Keywords in English
antibiotics
genomic library
glycosyltransferase
polyketide
regulator genes
Streptomyces olindensis
Abstract in English
Cosmomycin is an antitumoral antibiotic produced by the soil bacteria Streptomyces olindensis DAUFPE 5622. Gene expression studies established that stress condition genes like dnaJ and 18hsp, and cosmomycin biosynthetic pathways genes are expressed under antibiotic production. Also the genes cosS and cosY (unknowns function), were selected and analyzed by bioinformatics techniques attributing a transcriptional regulator and ornithine cyclodeaminase functions, respectively. A cassette was constructed in order to inactivate these two selected genes and generating void mutants. Another gene cosK, with glycosiltransferase function, also presented differences in its expression when the antibiotic is produced. We described in this work the presence of a hypothetical glycosiltransferase related with B-daunosamine daunomy, which transfers sugar molecules in the biosynthesis of daunomycin antibiotic.
 
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Publishing Date
2008-06-17
 
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