The calicheamicin gene cluster and its iterative type I enediyne PKS.
The enediynes exemplify nature's ingenuity. We have cloned and characterized the biosynthetic locus coding for perhaps the most notorious member of the nonchromoprotein enediyne family, calicheamicin. This gene cluster contains an unusual polyketide synthase (PKS) that is demonstrated to be essential for enediyne biosynthesis. Comparison of the calicheamicin locus with the locus encoding the chromoprotein enediyne C-1027 reveals that the enediyne PKS is highly conserved among these distinct enediyne families. Contrary to previous hypotheses, this suggests that the chromoprotein and nonchromoprotein enediynes are generated by similar biosynthetic pathways.
Laboratory for Biosynthetic Chemistry, Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI 53705, USA.
Joachim
J
Ahlert
Erica
E
Shepard
Natalia
N
Lomovskaya
Emmanuel
E
Zazopoulos
Alfredo
A
Staffa
Brian O
BO
Bachmann
Kexue
K
Huang
Leonid
L
Fonstein
Anne
A
Czisny
Ross E
RE
Whitwam
Chris M
CM
Farnet
Jon S
JS
Thorson
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D000903:Antibiotics, Antineoplastic / Q000096:biosynthesis*; D015139:Blotting, Southern; D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D017124:Conserved Sequence; D053281:Enediynes; D005798:Genes, Bacterial; D008847:Micromonospora / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D005810:Multigene Family; D009154:Mutation; D016366:Open Reading Frames; D016133:Polymerase Chain Reaction; D017434:Protein Structure, Tertiary; D017422:Sequence Analysis, DNA
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D053281:Enediynes; D009097:Multienzyme Complexes; C055955:calicheamicin gamma(1)I; C058024:C 1027