Identification of the Novobiocin Biosynthetic Gene Cluster of Streptomyces spheroides NCIB 11891
Autor: | Agnes Mühlenweg, Shu-Ming Li, Zhao-Xin Wang, Marion Steffensky, Lutz Heide |
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Rok vydání: | 2000 |
Předmět: |
DNA
Bacterial Molecular Sequence Data Biology Streptomyces Amide Synthases Gene cluster medicine Pharmacology (medical) Amino Acid Sequence Cloning Molecular ORFS Novobiocin Gene Library Antibacterial agent Pharmacology Sequence Homology Amino Acid Streptomycetaceae Chemistry Biosynthesis biochemical phenomena metabolism and nutrition Cosmids biology.organism_classification Molecular biology carbohydrates (lipids) Mutagenesis Insertional Open reading frame Infectious Diseases Genes Bacterial Multigene Family Heterologous expression medicine.drug |
Zdroj: | Antimicrobial Agents and Chemotherapy. 44:1214-1222 |
ISSN: | 1098-6596 0066-4804 |
DOI: | 10.1128/aac.44.5.1214-1222.2000 |
Popis: | The novobiocin biosynthetic gene cluster from Streptomyces spheroides NCIB 11891 was cloned by using homologous deoxynucleoside diphosphate (dNDP)-glucose 4,6-dehydratase gene fragments as probes. Double-stranded sequencing of 25.6 kb revealed the presence of 23 putative open reading frames (ORFs), including the gene for novobiocin resistance, gyrB r , and at least 11 further ORFs to which a possible role in novobiocin biosynthesis could be assigned. An insertional inactivation experiment with a dNDP-glucose 4,6-dehydratase fragment resulted in abolishment of novobiocin production, since biosynthesis of the deoxysugar moiety of novobiocin was blocked. Heterologous expression of a key enzyme of novobiocin biosynthesis, i.e., novobiocic acid synthetase, in Streptomyces lividans TK24 further confirmed the involvement of the analyzed genes in the biosynthesis of the antibiotic. |
Databáze: | OpenAIRE |
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