title: Expanding the structural diversity of polyketides by exploring the cofactor tolerance of an inline methyltransferase domain.
abstract: A strategy for introducing structural diversity into polyketides by exploiting the promiscuity of an in-line methyltransferase domain in a multidomain polyketide synthase is reported. In vitro investigations using the highly-reducing fungal polyketide synthase CazF revealed that its methyltransferase domain accepts the nonnatural cofactor propargylic Se-adenosyl-l-methionine and can transfer the propargyl moiety onto its growing polyketide chain. This propargylated polyketide product can then be further chain-extended and cyclized to form propargyl-α pyrone or be processed fully into the alkyne-containing 4'-propargyl-chaetoviridin A.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, California 90095, USA.
authors.forename: Jaclyn M
authors.initials: JM
authors.lastname: Winter
authors.forename: Grace
authors.initials: G
authors.lastname: Chiou
authors.forename: Ian R
authors.initials: IR
authors.lastname: Bothwell
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Neil K
authors.initials: NK
authors.lastname: Garg
authors.forename: Minkui
authors.initials: M
authors.lastname: Luo
authors.forename: Yi
authors.initials: Y
authors.lastname: Tang
mesh_terms: D000595:Amino Acid Sequence; D005663:Furans / Q000737:chemistry*; D008780:Methyltransferases / Q000737:chemistry*; D010293:Pargyline / Q000031:analogs & derivatives* / Q000737:chemistry*; D048630:Polyketide Synthases / Q000737:chemistry*; D061065:Polyketides / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D011753:Pyrones / Q000737:chemistry*
chemical_list: D005663:Furans; D061065:Polyketides; D011753:Pyrones; C579267:chaetoviridin A; D048630:Polyketide Synthases; D010293:Pargyline; D008780:Methyltransferases