Mutational Biosynthesis of Novel Rapamycins by a Strain of Streptomyces hygroscopicus NRRL 5491 Disrupted in rapL , Encoding a Putative Lysine Cyclodeaminase
| Autor: | James Staunton, Peter F. Leadlay, Lake Ee Khaw, Su M. Metcalfe, Günter A. Böhm |
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| Rok vydání: | 1998 |
| Předmět: |
Ammonia-Lyases
Magnetic Resonance Spectroscopy Mutant Genetics and Molecular Biology Polyenes Biology Microbiology Gas Chromatography-Mass Spectrometry Frameshift mutation chemistry.chemical_compound Biosynthesis Gene cluster Proline Frameshift Mutation Molecular Biology Gene Sirolimus chemistry.chemical_classification Cell Cycle biology.organism_classification Streptomyces Hydroxyproline Enzyme chemistry Biochemistry Genes Bacterial Multigene Family Pipecolic Acids Streptomyces hygroscopicus Immunosuppressive Agents |
| Zdroj: | Journal of Bacteriology. 180:809-814 |
| ISSN: | 1098-5530 0021-9193 |
| DOI: | 10.1128/jb.180.4.809-814.1998 |
| Popis: | The gene rapL lies within the region of the Streptomyces hygroscopicus chromosome which contains the biosynthetic gene cluster for the immunosuppressant rapamycin. Introduction of a frameshift mutation into rapL by ΦC31 phage-mediated gene replacement gave rise to a mutant which did not produce significant amounts of rapamycin. Growth of this rapL mutant on media containing added l -pipecolate restored wild-type levels of rapamycin production, consistent with a proposal that rapL encodes a specific l -lysine cyclodeaminase important for the production of the l -pipecolate precursor. In the presence of added proline derivatives, rapL mutants synthesized novel rapamycin analogs, indicating a relaxed substrate specificity for the enzyme catalyzing pipecolate incorporation into the macrocycle. |
| Databáze: | OpenAIRE |
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