title: In vitro analysis of carboxyacyl substrate tolerance in the loading and first extension modules of borrelidin polyketide synthase.
abstract: The borrelidin polyketide synthase (PKS) begins with a carboxylated substrate and, unlike typical decarboxylative loading PKSs, retains the carboxy group in the final product. The specificity and tolerance of incorporation of carboxyacyl substrate into type I PKSs have not been explored. Here, we show that the first extension module is promiscuous in its ability to extend both carboxyacyl and non-carboxyacyl substrates. However, the loading module has a requirement for substrates containing a carboxy moiety, which are not decarboxylated in situ. Thus, the loading module is the basis for the observed specific incorporation of carboxylated starter units by the borelidin PKS.
authors.affiliation: Department of Plant and Microbial Biology, ‡Department of Chemical and Biomolecular Engineering, §Department of Chemistry, ∥QB3 Institute, and ⊥Department of Bioengineering, University of California , Berkeley, California 94270, United States.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hagen
authors.forename: Sean
authors.initials: S
authors.lastname: Poust
authors.forename: Tristan
authors.initials: T
authors.lastname: de Rond
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yuzawa
authors.forename: Leonard
authors.initials: L
authors.lastname: Katz
authors.forename: Paul D
authors.initials: PD
authors.lastname: Adams
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Petzold
authors.forename: Jay D
authors.initials: JD
authors.lastname: Keasling
mesh_terms: D005233:Fatty Alcohols / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D048630:Polyketide Synthases / Q000235:genetics / Q000378:metabolism*; D061065:Polyketides / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D005233:Fatty Alcohols; D061065:Polyketides; C005066:borrelidin; D048630:Polyketide Synthases