Organizational and mutational analysis of a complete FR-008/candicidin gene cluster encoding a structurally related polyene complex.
The complete gene cluster for biosynthesis of a polyene complex, FR-008, spans 137.2 kb of the genome of Streptomyces sp. FR-008 consisting of six genes for a modular PKS and 15 additional genes. The extensive similarity to the partially characterized candicidin gene cluster in Streptomyces griseus IMRU3570, especially for genes involved in mycosamine biosynthesis, prompted us to compare the compounds produced by Streptomyces sp. FR-008 and Streptomyces griseus IMRU3570, and we found that FR-008 and candicidin complex are identical. A model for biosynthesis of a set of four structurally related FR-008/candicidin compounds was proposed. Deletion of the putative regulatory genes abolished antibiotic production, while disruption of putative glycosyltransferase and GDP-ketosugar aminotransferase functionalities led to the productions of a set of nonmycosaminated aglycones and a novel polyene complex with attachment of altered sugar moiety, respectively.
Chen
Shi
S
Bio-X Life Science Research Center and School of Life Science and Biotechnology, Shanghai Jiaotong University, 200030, Shanghai, China.
Huang
Xi
X
Zhou
Xiufen
X
Bai
Linquan
L
He
Jing
J
Jeong
Ki Jun
KJ
Lee
Sang Yup
SY
Deng
Zixin
Z
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002174:Candicidin / Q000737:chemistry / Q000378:metabolism*; D017931:DNA Primers; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005810:Multigene Family; D016366:Open Reading Frames; D011090:Polyenes / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013305:Streptomyces griseus / Q000201:enzymology / Q000235:genetics
D017931:DNA Primers; D009097:Multienzyme Complexes; D011090:Polyenes; D002174:Candicidin