A Cryptic Polyene Biosynthetic Gene Cluster in Streptomyces calvus Is Expressed upon Complementation with a Functional bldA Gene

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 muta...

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Published in:Chemistry & biology 2013-10, Vol.20 (10), p.1214-1224
Main Authors: Kalan, Lindsay, Gessner, Arne, Thaker, Maulik N., Waglechner, Nicholas, Zhu, XiMing, Szawiola, Anjuli, Bechthold, Andreas, Wright, Gerard D., Zechel, David L.
Format: Article
Language:English
Subjects:
Acyl Coenzyme A - metabolism
Amino Acid Sequence
Base Sequence
Gene Expression Regulation, Bacterial
Genes, Bacterial - genetics
Genetic Complementation Test
Ligases - chemistry
Ligases - genetics
Ligases - metabolism
Molecular Sequence Data
Multigene Family
Polyenes - metabolism
Spores, Bacterial
Streptomyces - genetics
Streptomyces - metabolism
Streptomyces - physiology
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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-tRNAUUA 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. [Display omitted] •Streptomyces calvus is a poor sporulator and exhibits a “bald” phenotype•Genome scanning revealed a point mutation in the bldA gene•Complementation with a correct bldA gene restored sporulation•Annimycin inhibits morphological differentiation in other Actinobacteria Streptomyces calvus has long been known to have a “bald”, non-sporulating phenotype. Kalan et al. reveal that the bald phenotype arises from a point of mutation in the bldA gene that encodes a misfolded tRNA molecule. With a correct bldA gene, sporulation is restored, and a cryptic polyketide was produced.
ISSN:1074-5521
1879-1301
DOI:10.1016/j.chembiol.2013.09.006