The dnrM gene in Streptomyces peucetius contains a naturally occurring frameshift mutation that is suppressed by another locus outside of the daunorubicin-production gene cluster.
A 2 center dot 7 kb BamHI fragment of the daunorubicin biosynthetic cluster in Streptomyces peucetius ATCC 29050 was shown to contain two ORFs, dnrL and dnrM, whose deduced products exhibit a high sequence similarity to a number of glucose-1-phosphate thymidylyl transferases and TDP-D-glucose dehydratases, respectively. Although these genes were believed to be necessary for the synthesis of the deoxyaminosugar, daunosamine, a constituent of daunorubicin, the dnrM gene contains a frameshift in the DNA sequence that causes the premature termination of translation. A gene encoding another TDP-glucose 4,6-dehydratase, previously isolated from S. peucetius, was identified by PCR amplification of genomic DNA. The presence of this gene explains why a dnrM::aphll mutation did not block daunorubicin production.
Gallo
Mark A
MA
School of Pharmacy, University of Wisconsin, Madison, Wl 53706, USA.
Ward
Joanne
J
School of Pharmacy, University of Wisconsin, Madison, Wl 53706, USA.
Hutchinson
C R
CR
Department of Bacteriology, University of Wisconsin, Madison, Wl 53706, USA.|School of Pharmacy, University of Wisconsin, Madison, Wl 53706, USA.
D000595:Amino Acid Sequence; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D003630:Daunorubicin / Q000096:biosynthesis*; D004926:Escherichia coli / Q000235:genetics; D016368:Frameshift Mutation; D005798:Genes, Bacterial; D016153:Genes, Suppressor; D006836:Hydro-Lyases / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family; D009713:Nucleotidyltransferases / Q000235:genetics; D016133:Polymerase Chain Reaction; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism
D017931:DNA Primers; D004269:DNA, Bacterial; D009713:Nucleotidyltransferases; C020587:glucose-1-phosphate thymidylyltransferase; D006836:Hydro-Lyases; C022771:dTDPglucose 4,6-dehydratase; D003630:Daunorubicin