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Enhancement of doxorubicin production by expression of structural sugar biosynthesis and glycosyltransferase genes inStreptomyces peucetius

Authors
Journal
Journal of Bioscience and Bioengineering
1389-1723
Publisher
Elsevier
Publication Date
Volume
108
Issue
2
Identifiers
DOI: 10.1016/j.jbiosc.2009.03.002
Keywords
  • Doxorubicin
  • Glycosyltransferase
  • Overproduction
  • Streptomyces Peucetius
  • Glucose-1-Phosphate Thymidylyltransferase
  • Tdp-D-Glucose 4
  • 6-Dehydratase

Abstract

Abstract To enhance doxorubicin (DXR) production, the structural sugar biosynthesis genes desIII and desIV from Streptomyces venezuelae ATCC 15439 and the glycosyltransferase pair dnrS/dnrQ from Streptomyces peucetius ATCC 27952 were cloned into the expression vector pIBR25, which contains a strong ermE⁎ promoter. The recombinant plasmids pDnrS25 and pDnrQS25 were constructed for overexpression of dnrS and the dnrS/dnrQ pair, whereas pDesSD25 and pDesQS25 were constructed to express desIII/desIV and dnrS/dnrQ–desIII/desIV, respectively. All of these recombinant plasmids were introduced into S. peucetius ATCC 27952. The recombinant strains produced more DXR than the S. peucetius parental strain: a 1.2-fold increase with pDnrS25, a 2.8-fold increase with pDnrQS25, a 2.6-fold increase with pDesSD25, and a 5.6-fold increase with pDesQS25. This study showed that DXR production was significantly enhanced by overexpression of potential biosynthetic sugar genes and glycosyltransferase.

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