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Title 

Expression of Streptomyces peucetius genes for doxorubicin resistance and aklavinone 11-hydroxylase in Streptomyces galilaeus ATCC 31133 and production of a hybrid aclacinomycin

Authors 

C K HwangHang Sub KimYoung Soo HongYoung Ho KimSoon Kwang HongS J KimJung Joon Lee

Publisher 

American Society for Microbiology

Issue Date 

1995

Citation 

Antimicrobial Agents and Chemotherapy, vol. 39, no. 7, pp. 1616-1620

Keywords 

11 hydroxyaclarubicinaclacinomycinaclarubicinaklavinoneaklavinone 11 hydroxylasedoxorubicinsteroid 11beta monooxygenaseunclassified drugantibiotic resistanceantineoplastic activity

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 doxurubicin, 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 tn a hybrid aclacinomycin A which showed highly specific in vitro cytotoxicity against leukemia and melanoma cell lines.

ISSN 

0066-4804

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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