Biomaterial Database

Cloning and expression of daunorubicin biosynthesis genes from Streptomyces peucetius and S. peucetius subsp. caesius. 1990

S L Otten, and K J Stutzman-Engwall, and C R Hutchinson

Department of Bacteriology, University of Wisconsin, Madison 53706.

Genes for the biosynthesis of daunorubicin (daunomycin) and doxorubicin (adriamycin), important antitumor drugs, were cloned from Streptomyces peucetius (the daunorubicin producer) and S. peucetius subsp. caesius (the doxorubicin producer) by use of the actI/tcmIa and actIII polyketide synthase gene probes. Restriction mapping and Southern analysis of the DNA cloned in a cosmid vector established that the DNA represented three nonoverlapping regions of the S. peucetius subsp. caesius genome. These three regions plus an additional one that hybridized to the same probes are present in the S. peucetius genome, as reported previously (K. J. Stutzman-Engwall and C. R. Hutchinson, Proc. Natl. Acad. Sci. USA 86:3135-3139, 1989). Functional analysis of representative clones from some of these regions in S. lividans, S. peucetius ATCC 29050, S. peucetius subsp. caesius ATCC 27952, and two of its blocked mutants (strains H6101 and H6125) showed that many of the antibiotic production genes reside in the region of DNA represented by the group IV clones. This conclusion is based on the production of epsilon-rhodomycinone, a key intermediate of the daunorubicin pathway, in certain S. lividans transformants and on the apparent complementation of mutations that block daunorubicin biosynthesis in strains H6101 and H6125. Some of the transformants of strains 29050, 27952, and H6125 exhibited substantial overproduction of epsilon-rhodomycinone and daunorubicin.

UI	MeSH Term	Description	Entries
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D003001	Cloning, Molecular	The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.	Molecular Cloning
D003630	Daunorubicin	A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of LEUKEMIA and other NEOPLASMS.	Daunomycin,Rubidomycin,Rubomycin,Cerubidine,Dauno-Rubidomycine,Daunoblastin,Daunoblastine,Daunorubicin Hydrochloride,NSC-82151,Dauno Rubidomycine,Hydrochloride, Daunorubicin,NSC 82151,NSC82151
D005798	Genes, Bacterial	The functional hereditary units of BACTERIA.	Bacterial Gene,Bacterial Genes,Gene, Bacterial
D005816	Genetic Complementation Test	A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell.	Allelism Test,Cis Test,Cis-Trans Test,Complementation Test,Trans Test,Allelism Tests,Cis Tests,Cis Trans Test,Cis-Trans Tests,Complementation Test, Genetic,Complementation Tests,Complementation Tests, Genetic,Genetic Complementation Tests,Trans Tests
D000903	Antibiotics, Antineoplastic	Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms.	Antineoplastic Antibiotics,Cytotoxic Antibiotics,Antibiotics, Cytotoxic
D013302	Streptomyces	A genus of bacteria that form a nonfragmented aerial mycelium. Many species have been identified with some being pathogenic. This genus is responsible for producing a majority of the ANTI-BACTERIAL AGENTS of practical value.
D015870	Gene Expression	The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.	Expression, Gene,Expressions, Gene,Gene Expressions
D018943	Anthracyclines	Organic compounds that have a tetrahydronaphthacenedione ring structure attached by a glycosidic linkage to the amino sugar daunosamine.	Anthracycline