• JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
 
  Bookmark and Share
 
 
Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2019.tde-09122021-125029
Document
Author
Full name
Ruth Elizabeth Ortiz Castro
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2019
Supervisor
Committee
Maldonado, Gabriel Padilla (President)
Gomes, Claudiana Lameu
Jimenez, Paula Christine
Lotufo, Leticia Veras Costa
Silva, Luiziana Ferreira da
Title in Portuguese
Caracterização de genes putativos biossintéticos do antitumoral cosmomicina D.
Keywords in Portuguese
Streptomyces olindensis
antraciclinas
cluster biossintético
cosmomicina
gene regulador
Abstract in Portuguese
Streptomyces olindensis DAUFPE 5622 foi isolado na década de 1960 a partir de uma amostra de solo brasileira. Produz a antraciclina cosmomicina D, que tem atividade antitumoral e atraiu interesse por causa de seu padrão peculiar de glicosilação. Após anos de estudos sobre a molécula da cosmomicina e sua via biossintética, o estudo do cluster genético permitiu identificar os produtos codificados em cada ORF e agrupá-los, de acordo com sua funcionalidade, em genes envolvidos na biossíntese de agliconas, modificação da aglicona, biossíntese de açúcares, glicosiltransferases, genes de resistência e genes com função desconhecida. Entretanto o tamanho exato do cluster e o número de genes permaneceram desconhecidos. Neste estudo concluímos que o cluster biossintético da cosmomicina D em Streptomyces olindensis é constituído por 38 ORFs, tendo como extremos definidos ORF17 cosU e ORF54 cosV G1Pdt (glicose-1-fosfato-timidiltransferase); e que o cluster da cosmomicina tem um tamanho de aproximadamente 40 kb (39,972 pb). Estudamos também os genes cosY e cosM. Quando cosY foi inativado, a produção de cosmomicina aumentou, indicando uma potencial atividade reguladora. Para cosK, a inativação produziu um desvio na via biossintética levando à síntese de substâncias possivelmente inéditas. Estudos adicionais são necessários para estabelecer a real função desses dois genes.
Title in English
Characterization of putative biosynthetic genes of the antitumor cosmomycin D.
Keywords in English
Streptomyces olindensis
anthracyclines
biosynthetic cluster
cosmomycin
regulatory gene
Abstract in English
Streptomyces olindensis DAUFPE 5622 was isolated in the 1960s from a Brazilian soil sample. It produces the anthracycline cosmomycin D, which has antitumor activity and has attracted interest because of its distinctive glycosylation pattern. After many years and studies on the cosmomycin molecule and its biosynthetic pathway, the study of the gene cluster has allowed to identify the products encoded by each ORF and grouped them according to their functionality in genes involved in aglycone biosynthesis, aglycone modification, sugar biosynthesis, glycosyltransferases, resistance genes and genes with unknown function. However, the exact size of the cluster and number of genes remained unknown. In this study we can conclude that the cosmomycin D cluster in Streptomyces olindensis is comprised of 38 ORFs, having as defined ends ORF17 cosU and ORF54 cosV G1Pdt (glucose-1-phosphate thymidyltransferase); and that the cosmomycin cluster has a size of approximately 40Kb (39.972bp). We also studied the cosY and cosM genes. When cosY was inactivated the production of cosmomycin increased, indicating a potential regulatory activity. The cosK inactivation lead to a deviation in the biosynthetic pathway leading to the synthesis of probably new substances. Additional studies are necessary to establish the real functions of these two genes.
 
WARNING - Viewing this document is conditioned on your acceptance of the following terms of use:
This document is only for private use for research and teaching activities. Reproduction for commercial use is forbidden. This rights cover the whole data about this document as well as its contents. Any uses or copies of this document in whole or in part must include the author's name.
Publishing Date
2022-01-07
 
WARNING: Learn what derived works are clicking here.
All rights of the thesis/dissertation are from the authors
CeTI-SC/STI
Digital Library of Theses and Dissertations of USP. Copyright © 2001-2024. All rights reserved.