title: Structural insight into chain-length control and product specificity of pentaketide chromone synthase from Aloe arborescens.
abstract: The crystal structures of a wild-type and a mutant PCS, a novel plant type III polyketide synthase from a medicinal plant, Aloe arborescens, were solved at 1.6 A resolution. The crystal structures revealed that the pentaketide-producing wild-type and the octaketide-producing M207G mutant shared almost the same overall folding, and that the large-to-small substitution dramatically increases the volume of the polyketide-elongation tunnel by opening a gate to two hidden pockets behind the active site of the enzyme. The chemically inert active site residue 207 thus controls the number of condensations of malonyl-CoA, solely depending on the steric bulk of the side chain. These findings not only provided insight into the polyketide formation reaction, but they also suggested strategies for the engineered biosynthesis of polyketides.
authors.affiliation: Mitsubishi Kagaku Institute of Life Sciences (MITILS), 11 Minamiooya, Machida, Tokyo 194-8511, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Morita
authors.forename: Shin
authors.initials: S
authors.lastname: Kondo
authors.forename: Satoshi
authors.initials: S
authors.lastname: Oguro
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Noguchi
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Sugio
authors.forename: Ikuro
authors.initials: I
authors.lastname: Abe
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kohno
mesh_terms: D000504:Aloe / Q000201:enzymology* / Q000235:genetics; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001665:Binding Sites; D002867:Chromones; D018360:Crystallography, X-Ray; D019281:Dimerization; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D048630:Polyketide Synthases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D016415:Sequence Alignment
chemical_list: D002867:Chromones; D048630:Polyketide Synthases