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.
Kwon
Hyung-Jin
HJ
Division of Pharmaceutical Sciences and, Department of Chemistry, University of Wisconsin, Madison, WI 53705, USA.
Smith
Wyatt C
WC
Scharon
A Janelle
AJ
Hwang
Sung Hee
SH
Kurth
Mark J
MJ
Shen
Ben
B
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