Biosynthesis of the enediyne antitumor antibiotic C-1027.
C-1027 is a potent antitumor agent with a previously undescribed molecular architecture and mode of action. Cloning and characterization of the 85-kilobase C-1027 biosynthesis gene cluster from Streptomyces globisporus revealed (i) an iterative type I polyketide synthase that is distinct from any bacterial polyketide synthases known to date, (ii) a general polyketide pathway for the biosynthesis of both the 9- and 10-membered enediyne antibiotics, and (iii) a convergent biosynthetic strategy for the C-1027 chromophore from four building blocks. Manipulation of genes governing C-1027 biosynthesis allowed us to produce an enediyne compound in a predicted manner.
Liu
Wen
W
Division of Pharmaceutical Sciences, University of Wisconsin, Madison, WI 53705, USA.
Christenson
Steven D
SD
Standage
Scott
S
Shen
Ben
B
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D000903:Antibiotics, Antineoplastic / Q000096:biosynthesis*; D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D053281:Enediynes; D005798:Genes, Bacterial; D009097:Multienzyme Complexes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005810:Multigene Family; D009154:Mutation; D016366:Open Reading Frames; D017434:Protein Structure, Tertiary; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D053281:Enediynes; D009097:Multienzyme Complexes; C058024:C 1027