C-O bond formation by polyketide synthases.
Polyketide synthases (PKSs) assemble the polyketide carbon backbone by sequential decarboxylative condensation of acyl coenzyme A (CoA) precursors, and the C-C bond-forming step in this process is catalyzed by the beta-ketoacyl synthase (KS) domain or subunit. Genetic and biochemical characterization of the nonactin biosynthesis gene cluster from Streptomyces griseus revealed two KSs, NonJ and NonK, that are highly homologous to known KSs but catalyze sequential condensation of the acyl CoA substrates by forming C-O rather than C-C bonds. This chemistry can be used in PKS engineering to increase the scope and diversity of polyketide biosynthesis.
Division of Pharmaceutical Sciences and, Department of Chemistry, University of Wisconsin, Madison, WI 53705, USA.
Hyung-Jin
HJ
Kwon
Wyatt C
WC
Smith
A Janelle
AJ
Scharon
Sung Hee
SH
Hwang
Mark J
MJ
Kurth
Ben
B
Shen
D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase / Q000737:chemistry* / Q000378:metabolism*; D000214:Acyl Coenzyme A / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D005798:Genes, Bacterial; D018942:Macrolides / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000378:metabolism*; D005810:Multigene Family; D009154:Mutation; D015202:Protein Engineering; D021122:Protein Subunits; D016415:Sequence Alignment; D021241:Spectrometry, Mass, Electrospray Ionization; D013302:Streptomyces / Q000235:genetics; D013305:Streptomyces griseus / Q000201:enzymology* / Q000235:genetics; D014169:Transformation, Bacterial
D000214:Acyl Coenzyme A; D018942:Macrolides; D009097:Multienzyme Complexes; D021122:Protein Subunits; D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase; C050476:nonactin