New anthracycline metabolites produced by the aklavinone 11-hydroxylase gene in Streptomyces galilaeus ATCC 31133.
Transformation of Streptomyces galilaeus ATCC 31133 with the aklavinone 11-hydroxylase gene (dnrF) resulted in the production of many red pigments. The new metabolites were purified and their structures were determined as 11-hydroxylated aclacinomycin A, B and T by spectral analysis. This result indicated that the dnrF was stably expressed in the strain S. galilaeus ATCC 31133 to give rise to hybrid aclacinomycins. In addition, a new aclacinomycin analog named 11-hydroxyaclacinomycin X was isolated from the same culture. Its structure was elucidated as 2"'-amino-11-hydroxyaclacinomycin Y. It showed strong cytotoxicity against several human tumor cell lines, especially leukemia and melanoma cell lines.
Kim
H S
HS
Korea Research Institute of Bioscience and Biotechnology, KIST, Taejon, Korea.
Hong
Y S
YS
Kim
Y H
YH
Yoo
O J
OJ
Lee
J J
JJ
D015250:Aclarubicin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D018943:Anthracyclines / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D015394:Molecular Structure; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism
C099664:11-hydroxyaclacinomycin X; D018943:Anthracyclines; D000970:Antineoplastic Agents; C011157:aclacinomycins; D015250:Aclarubicin; C090407:aklavinone 11-hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases