Expression of Streptomyces peucetius genes for doxorubicin resistance and aklavinone 11-hydroxylase in Streptomyces galilaeus ATCC 31133 and production of a hybrid aclacinomycin.
Antimicrob Agents Chemother
; 39(7): 1616-20, 1995 Jul.
Article
em En
| MEDLINE
| ID: mdl-7492117
ABSTRACT
The aklavinone 11-hydroxylase gene and two doxorubicin resistance genes cloned from Streptomyces peucetius subsp. caesius ATCC 27952 were introduced into doxorubicin-sensitive Streptomyces galilaeus ATCC 31133, an aclacinomycin producer. The doxorubicin resistance genes drrA and drrB endowed S. galilaeus with high-level resistance to doxorubicin, indicating that the resistance mechanism for doxorubicin might be different from that for aclacinomycin A. Transformation of S. galilaeus ATCC 31133 with plasmid pMC213 containing the aklavinone 11-hydroxylase gene (dnrF) resulted in the production of many red pigments. A new metabolite was purified, and the position of the newly introduced hydroxyl group was determined. This result indicated that the aklavinone 11-hydroxylase gene was stably expressed in S. galilaeus ATCC 31133 and that it gave rise to a hybrid aclacinomycin A which showed highly specific in vitro cytotoxicity against leukemia and melanoma cell lines.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Streptomyces
/
Aclarubicina
/
Doxorrubicina
/
Genes Bacterianos
Limite:
Humans
Idioma:
En
Ano de publicação:
1995
Tipo de documento:
Article