title: Characterization of FK506 biosynthetic intermediates involved in post-PKS elaboration.
abstract: The post-PKS modification steps of FK506 biosynthesis include C9-oxidation and 31-O-methylation, but the sequence of these reactions and the exact route have remained unclear. This study details the post-PKS modification pathways in FK506 biosynthesis through the identification of all intermediates and in vitro enzymatic reactions of the cytochrome P450 hydroxylase FkbD and the methyltransferase FkbM. These results complete our understanding of post-PKS modification steps to FK506 showing the substrate flexibility of two enzymes involved and the existence of two parallel biosynthetic routes to FK506.
authors.affiliation: Department of Chemistry and Nano Science, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Yeon Hee
authors.initials: YH
authors.lastname: Ban
authors.forename: Pramod B
authors.initials: PB
authors.lastname: Shinde
authors.forename: Jae-Yeon
authors.initials: JY
authors.lastname: Hwang
authors.forename: Myoung-Chong
authors.initials: MC
authors.lastname: Song
authors.forename: Dong Hwan
authors.initials: DH
authors.lastname: Kim
authors.forename: Si-Kyu
authors.initials: SK
authors.lastname: Lim
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Sohng
authors.forename: Yeo Joon
authors.initials: YJ
authors.lastname: Yoon
mesh_terms: D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D008780:Methyltransferases / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D015394:Molecular Structure; D009097:Multienzyme Complexes / Q000737:chemistry / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D010084:Oxidation-Reduction; D048630:Polyketide Synthases / Q000378:metabolism*; D013302:Streptomyces / Q000201:enzymology* / Q000378:metabolism; D016559:Tacrolimus / Q000378:metabolism*
chemical_list: D009097:Multienzyme Complexes; D048630:Polyketide Synthases; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D008780:Methyltransferases; D016559:Tacrolimus