The gene cluster for fluorometabolite biosynthesis in Streptomyces cattleya: a thioesterase confers resistance to fluoroacetyl-coenzyme A.
A genomic library of Streptomyces cattleya was screened to isolate a gene cluster encoding enzymes responsible for the production of fluorine-containing metabolites. In addition to the previously described fluorinase FlA which catalyzes the formation of 5'-fluoro-5'-deoxyadenosine from S-adenosylmethionine and fluoride, 11 other putative open reading frames have been identified. Three of the proteins encoded by these genes have been characterized. FlB was determined to be the second enzyme in the pathway, catalyzing the phosphorolytic cleavage of 5'-fluoro-5'-deoxyadenosine to produce 5-fluoro-5-deoxy-D-ribose-1-phosphate. The enzyme FlI was found to be an S-adenosylhomocysteine hydrolase, which may act to relieve S-adenosylhomocysteine inhibition of the fluorinase. Finally, flK encodes a thioesterase which catalyzes the selective breakdown of fluoroacetyl-CoA but not acetyl-CoA, suggesting that it provides the producing strain with a mechanism for resistance to fluoroacetate.
Huang
Fanglu
F
University Chemical Laboratory, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, United Kingdom.
Haydock
Stephen F
SF
Spiteller
Dieter
D
Mironenko
Tatiana
T
Li
Tsung-Lin
TL
O'Hagan
David
D
Leadlay
Peter F
PF
Spencer
Jonathan B
JB
D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000595:Amino Acid Sequence; D001483:Base Sequence; D002384:Catalysis; D017931:DNA Primers; D004950:Esterases / Q000235:genetics / Q000378:metabolism*; D017611:Fluorine Compounds / Q000378:metabolism*; D005798:Genes, Bacterial; D008969:Molecular Sequence Data; D005810:Multigene Family; D016366:Open Reading Frames; D017386:Sequence Homology, Amino Acid; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism
D017931:DNA Primers; D017611:Fluorine Compounds; C031696:fluoroacetyl-coenzyme A; D000105:Acetyl Coenzyme A; D004950:Esterases