The candicidin gene cluster from Streptomyces griseus IMRU 3570.
A 205 kb DNA region from Streptomyces griseus IMRU 3570, including the candicidin biosynthetic gene cluster, was cloned and partially sequenced. Analysis of the sequenced DNA led to identification of genes encoding part of a modular polyketide synthase (PKS), genes for thioesterase, macrolactone ring modification, mycosamine biosynthesis and attachment to the macrolide ring, candicidin export and regulatory proteins. It represents the first extensive genetic characterization of an aromatic polyene macrolide antibiotic biosynthetic gene cluster. Of particular interest is the presence of the CanP1 loading domain (the first described as responsible for the activation of an aromatic starter unit) and the polypeptide CanP3 (carrying modules for the formation of five out of seven conjugated double bonds). Disruption of the pabAB gene that encodes the starter unit of candicidin abolished its production [which was restored when exogenous p-aminobenzoic acid (PABA) was supplied to the culture] and resulted in an enhanced production of another antifungal compound that is barely detected in the wild-type.
Campelo
Ana Belén
AB
Departamento de Ecologı́a, Genética y Microbiologı́a, Área de Microbiologı́a, Facultad de Biologı́a, Universidad de León, 24071 León, Spain1.
Gil
José A
JA
Departamento de Ecologı́a, Genética y Microbiologı́a, Área de Microbiologı́a, Facultad de Biologı́a, Universidad de León, 24071 León, Spain1.
D000935:Antifungal Agents / Q000096:biosynthesis*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D002174:Candicidin / Q000096:biosynthesis*; D003001:Cloning, Molecular; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D006595:Hexosamines / Q000096:biosynthesis / Q000235:genetics; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D005810:Multigene Family; D015183:Restriction Mapping; D013305:Streptomyces griseus / Q000235:genetics* / Q000378:metabolism
D000935:Antifungal Agents; D001426:Bacterial Proteins; D006595:Hexosamines; D009097:Multienzyme Complexes; D002174:Candicidin; C014692:mycosamine