title: A cryptic polyene biosynthetic gene cluster in Streptomyces calvus is expressed upon complementation with a functional bldA gene.
abstract: 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.
authors.affiliation: Michael G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Kalan
authors.forename: Arne
authors.initials: A
authors.lastname: Gessner
authors.forename: Maulik N
authors.initials: MN
authors.lastname: Thaker
authors.forename: Nicholas
authors.initials: N
authors.lastname: Waglechner
authors.forename: Ximing
authors.initials: X
authors.lastname: Zhu
authors.forename: Anjuli
authors.initials: A
authors.lastname: Szawiola
authors.forename: Andreas
authors.initials: A
authors.lastname: Bechthold
authors.forename: Gerard D
authors.initials: GD
authors.lastname: Wright
authors.forename: David L
authors.initials: DL
authors.lastname: Zechel
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D000595:Amino Acid Sequence; D001483:Base Sequence; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial / Q000235:genetics*; D005816:Genetic Complementation Test; D008025:Ligases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family; D011090:Polyenes / Q000378:metabolism*; D013171:Spores, Bacterial; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology
chemical_list: D000214:Acyl Coenzyme A; D011090:Polyenes; D008025:Ligases