A Cryptic Polyene Biosynthetic Gene Cluster in Streptomyces calvus Is Expressed upon Complementation with a Functional bldA Gene
| Autor: | Nicholas Waglechner, Xi Ming Zhu, Gerard D. Wright, Maulik N. Thaker, David L. Zechel, Lindsay Kalan, Andreas Bechthold, Arne Gessner, Anjuli Szawiola |
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| Rok vydání: | 2013 |
| Předmět: |
Molecular Sequence Data
Clinical Biochemistry Polyenes 01 natural sciences Biochemistry DNA sequencing Ligases 03 medical and health sciences Polyketide synthase Drug Discovery Gene cluster Streptomyces calvus Amino Acid Sequence Molecular Biology Gene 030304 developmental biology Spores Bacterial Pharmacology Genetics 0303 health sciences Base Sequence biology 010405 organic chemistry Point mutation Genetic Complementation Test fungi Gene Expression Regulation Bacterial General Medicine Phenotype Streptomyces 0104 chemical sciences Complementation Genes Bacterial Multigene Family biology.protein Molecular Medicine Acyl Coenzyme A |
| Zdroj: | Chemistry & Biology. 20:1214-1224 |
| ISSN: | 1074-5521 |
| Popis: | Summary Streptomyces calvus is best known as the producer of the fluorinated natural product nucleocidin. This strain of Streptomycetes is also unusual for displaying a "bald" phenotype that is deficient in the formation of aerial mycelium and spores. Genome sequencing of this organism revealed a point mutation in the bldA gene that is predicted to encode a misfolded Leu-tRNA UUA molecule. Complementation of S. calvus with a correct copy of bldA restored sporulation and additionally promoted production of a polyeneoic acid amide, 4- Z -annimycin, and a minor amount of the isomer, 4- E -annimycin. Bioassays reveal that these compounds inhibit morphological differentiation in other Actinobacteria. The annimycin gene cluster encoding a type 1 polyketide synthase was identified and verified through disruption studies. This study underscores the importance of the bldA gene in regulating the expression of cryptic biosynthetic genes. |
| Databáze: | OpenAIRE |
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