EXPRESSION OF STREPTOMYCES-PEUCETIUS GENES FOR DOXORUBICIN RESISTANCEAND AKLAVINONE 11-HYDROXYLASE IN STREPTOMYCES-GALILAEUS ATCC-31133 AND PRODUCTION OF A HYBRID ACLACINOMYCIN

The aklavinone 11-hydroxylase gene and two doxorubicin resistance gene s cloned from Streptomyces peucetius subsp. caesius ATCC 27952 were in troduced 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, i ndicating that the resistance mechanism for doxorubicin might be diffe rent from that for aclacinomycin A. Transformation of S. galilaeus ATC C 31133 with plasmid pMC213 containing the aklavinone 11-hydroxylase g ene (dnrF) resulted in the production of many red pigments. A new meta bolite was purified, and the position of the newly introduced hydroxyl group was determined. This result indicated that the aklavinone 11-hy droxylase gene was stably expressed in S. galilaeus ATCC 31133 and tha t it gave rise to a hybrid aclacinomycin A which showed highly specifi c in vitro cytotoxicity against leukemia and melanoma cell lines.