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

• Published in: Microbiology (Society for General Microbiology) 1996-02, Vol.142 (2), p.269-275
• Main Authors: Gallo, Mark A, Ward, Joanne, Hutchinson, C. R
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Bacteriology; Base Sequence; Biological and medical sciences; Daunorubicin - biosynthesis; DNA Primers - genetics; DNA, Bacterial - genetics; Escherichia coli - genetics; Frameshift Mutation; Fundamental and applied biological sciences. Psychology; Genes, Bacterial; Genes, Suppressor; Genetics; Hydro-Lyases - genetics; Microbiology; Molecular Sequence Data; Multigene Family; Nucleotidyltransferases - genetics; Polymerase Chain Reaction; Streptomyces - genetics; Streptomyces - metabolism; Streptomyces peucetius
• ISSN: 1350-0872; 1465-2080
• DOI: 10.1099/13500872-142-2-269

1 School of Pharmacy, University of Wisconsin, Madison, Wl 53706, USA 2 Department of Bacteriology, University of Wisconsin, Madison, Wl 53706, USA ABSTRACT Summary: A 2.7 kb Bam HI 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. Author for correspondence: C.R. Hutchinson. Tel: [phone]. Fax: [phone]. e-mail: [e-mail] Keywords: daunosamine, deoxyamino sugar, inactive gene, TDP-D-glucose 4,6-dehydratase, glucose-l-phosphate thymidylyl transferase Present address: Sandoz Clinical Development Centre, The Quadrangle, Frimley Business Park, Frimley, Camberley, Surrey, GU16 5SQ, UK.