원문정보
초록
영어
The doxorubicin biosynthetic gene cluster in Streptomyces peucetius ATCC 27952 was found to contain a TDP-D-glucose 4,6-dehydratase gene, dnsM, putatively involved in the biosynthesis of 2,3,6-trideoxy-3-aminohexose, daunosamine. But the gene contains a frameshift in the DNA sequence that caused the premature termination of translation. In pursuit of another TDP-D-glucose dehydratase in S. peucetius, we discovered a homologue gene, rmbB, whose deduced product exhibit a high sequence similarity to a number of TDP-D-glucose 4,6-dehydratases. The gene was found to be located within a putative rhamnose biosynthetic gene cluster at another locus of the genome. The rmbB protein was verified to be functional by enzyme assay as it converted TDP-D-glucose into TDP-4-dehydro-6-deoxy-D-glucose. Inactivation of rmbB from S. peucetius genome abolished the production of doxorubicin. Consequently, rmbB was proved to be essential for the biosynthesis of doxorubicin.