title: Chain elongation and cyclization in type III PKS DpgA.
abstract: Chain elongation and cyclization of precursors of dihydroxyphenylacetyl-CoA (DPA-CoA) catalyzed by the bacterial type III polyketide synthase DpgA were studied. Two labile intermediates, di- and tri-ketidyl-CoA (DK- and TK-CoA), were proposed and chemically synthesized. In the presence of DpgABD, each of these with [(13)C(3)]malonyl-CoA (MA-CoA) was able to form partially (13)C-enriched DPA-CoA. By NMR and MS analysis, the distribution of (13)C atoms in the partially (13)C-enriched DPA-CoA shed light on how the polyketide chain elongates and cyclizes in the DpgA-catalyzed reaction. Polyketone intermediates elongate in a manner different from that which had been believed: two molecules of DK-CoA, or one DK-CoA plus one acetoacetyl-CoA (AA-CoA), but not two molecules of AA-CoA can form one molecule of DPA-CoA. As a result, polyketidyl-CoA serves as both the starter and extender, whereas polyketone-CoA without the terminal carboxyl group can only act as an extender. The terminal carboxyl group is crucial for the cyclization that likely takes place on CoA.
authors.affiliation: Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, PR China.
authors.forename: Hai-Chen
authors.initials: HC
authors.lastname: Wu
authors.forename: Yi-San
authors.initials: YS
authors.lastname: Li
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Liu
authors.forename: Syue-Yi
authors.initials: SY
authors.lastname: Lyu
authors.forename: Chang-Jer
authors.initials: CJ
authors.lastname: Wu
authors.forename: Tsung-Lin
authors.initials: TL
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D002384:Catalysis; D003500:Cyclization; D008969:Molecular Sequence Data; D048630:Polyketide Synthases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D048630:Polyketide Synthases