Dickens M L, Strohl W R
Department of Microbiology, The Ohio State University, Columbus, 43210, USA.
J Bacteriol. 1996 Jun;178(11):3389-95. doi: 10.1128/jb.178.11.3389-3395.1996.
DNA sequence analysis of a region of the Streptomyces sp. strain C5 daunomycin biosynthesis gene cluster, located between the daunomycin polyketide biosynthesis gene cluster and a dnrI (transcriptional activator) homolog, revealed the presence of a gene encoding a P-450-like enzyme with a deduced Mr of 46,096. Expression of this gene, named herein doxA, in Streptomyces lividans TY24 resulted in in vivo bioconversion of daunomycin to doxorubicin. DoxA showed specificity for only daunomycin and 13-dihydrodaunomycin, both of which were converted to doxorubicin. Daunomycinone (daunomycin aglycone), carminomycin, 13-dihydrocarminomycin, idarubicin, and aklavin were not apparent substrates for DoxA. In vector controls or in vectors in which doxA was poorly expressed, S. lividans catalyzed the reduction of daunomycin and other 13-oxo-anthracyclines and -anthracyclinones to their 13-dihydro homologs.
对链霉菌属菌株C5柔红霉素生物合成基因簇的一个区域进行DNA序列分析，该区域位于柔红霉素聚酮生物合成基因簇和一个dnrI（转录激活因子）同源物之间，结果显示存在一个编码P - 450样酶的基因，推导的Mr为46,096。这个在此命名为doxA的基因在变铅青链霉菌TY24中表达，导致柔红霉素在体内生物转化为阿霉素。DoxA仅对柔红霉素和13 - 二氢柔红霉素具有特异性，二者均被转化为阿霉素。柔红霉酮（柔红霉素糖苷配基）、洋红霉素、13 - 二氢洋红霉素、伊达比星和阿克拉霉素不是DoxA的明显底物。在载体对照或doxA表达不佳的载体中，变铅青链霉菌催化柔红霉素和其他13 - 氧代蒽环类和蒽环酮类还原为它们的13 - 二氢同源物。
