title: A dehydratase domain in ambruticin biosynthesis displays additional activity as a pyran-forming cyclase.
abstract: Hydropyran rings are a common structural motif in reduced polyketides. Information on their biosynthetic formation and particularly the biochemical characterization of the responsible enzymes has only been reported in few cases. The dehydratase domain AmbDH3 from the ambruticin polyketide synthase was investigated. Through in vitro assay of the recombinant domain with synthetically-derived substrate surrogates, it was shown that it has a second catalytic activity as a cyclase that performs oxa-conjugate addition. Probing AmbDH3 with synthetic substrate analogues revealed stereoselectivity and substrate tolerance in both substeps. This is the first characterization of a pyran-forming cyclase from a cis-AT PKS system and the first report of a polyketide synthase domain with this kind of dual activity. Finally, it was revealed that this domain shows potential for application in chemoenzymatic synthesis.
authors.affiliation: Institut für Organische Chemie, Leibniz Universität Hannover, Schneiderberg 1 B, 30167 Hannover (Germany) http://uhw3dev.uni-hannover.de/oci/de/arbeitskreise/hahn/index.php.
authors.forename: Gesche
authors.initials: G
authors.lastname: Berkhan
authors.forename: Frank
authors.initials: F
authors.lastname: Hahn
mesh_terms: D004789:Enzyme Activation; D006836:Hydro-Lyases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008968:Molecular Conformation; D011714:Pyrans / Q000737:chemistry / Q000378:metabolism
chemical_list: D011714:Pyrans; D006836:Hydro-Lyases; C014964:ambruticin
keywords: biocatalysis; cyclases; dehydratases; heterocycles; polyketides