Cholesterol oxidases act as signaling proteins for the biosynthesis of the polyene macrolide pimaricin.
The gene cluster responsible for pimaricin biosynthesis in Streptomyces natalensis contains a cholesterol oxidase-encoding gene (pimE) surrounded by genes involved in pimaricin production. Gene-inactivation and -complementation experiments revealed that pimE encodes a functional cholesterol oxidase and, surprisingly, that it is also involved in pimaricin biosynthesis. This extracellular enzyme was purified from S. natalensis culture broths to homogeneity, and it was shown to restore pimaricin production when added to the mutant culture broths. Other cholesterol oxidases also triggered pimaricin production, suggesting that these enzymes could act as signaling proteins for polyene biosynthesis. This finding constitutes the description of a cholesterol oxidase gene with an involvement in antibiotic biosynthesis, and it broadens the scope of the biological functions for this type of oxidase.
Mendes
Marta V
MV
Instituto de Biotecnología INBIOTEC, 24006 León, Spain.
Recio
Eliseo
E
Antón
Nuria
N
Guerra
Susana M
SM
Santos-Aberturas
Javier
J
Martín
Juan F
JF
Aparicio
Jesús F
JF
D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000378:metabolism*; D002789:Cholesterol Oxidase / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D005810:Multigene Family; D016296:Mutagenesis; D010866:Natamycin / Q000096:biosynthesis*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014158:Transcription, Genetic
D000935:Antifungal Agents; D010866:Natamycin; D002789:Cholesterol Oxidase