title: Stereospecific prenylation of tryptophan by a cyanobacterial post-translational modification enzyme.
abstract: Prenylation is a key post-translational reaction to increase the structural diversity and bioactivity of peptides and proteins. Until now, only one post-translational modification enzyme, ComQ, has been identified to mediate the prenylation of a tryptophan residue in ribosomally synthesized peptides. Here, we report the in vitro characterization of KgpF, a novel prenyltransferase which transfers dimethylallyl moieties to tryptophan residues during kawaguchipeptin A biosynthesis. The stereospecific prenylation by KgpF was determined by a combination of in vitro dimethylallylation of Fmoc-tryptophan by KgpF and chemical synthesis of dimethylallylated Fmoc-tryptophan diastereomers. KgpF modified the tryptophan derivative with a dimethylallyl group at the 3 position of its indole ring, resulting in the formation of a tricyclic structure with the same scaffold as prenylation by ComQ, but with the opposite stereochemistry.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. abei@mol.f.u-tokyo.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Okada
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. abei@mol.f.u-tokyo.ac.jp.
authors.forename: Tomotoshi
authors.initials: T
authors.lastname: Sugita
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. abei@mol.f.u-tokyo.ac.jp.
authors.forename: Kohei
authors.initials: K
authors.lastname: Akita
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. abei@mol.f.u-tokyo.ac.jp.
authors.forename: Yu
authors.initials: Y
authors.lastname: Nakashima
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. abei@mol.f.u-tokyo.ac.jp.
authors.forename: Tian
authors.initials: T
authors.lastname: Tian
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. abei@mol.f.u-tokyo.ac.jp.
authors.forename: Chang
authors.initials: C
authors.lastname: Li
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. abei@mol.f.u-tokyo.ac.jp.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Mori
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. abei@mol.f.u-tokyo.ac.jp.
authors.forename: Ikuro
authors.initials: I
authors.lastname: Abe
mesh_terms: D000458:Cyanobacteria / Q000201:enzymology*; D004122:Dimethylallyltranstransferase / Q000378:metabolism*; D005449:Fluorenes / Q000737:chemistry; D017368:Protein Prenylation; D011499:Protein Processing, Post-Translational; D013237:Stereoisomerism; D014364:Tryptophan / Q000378:metabolism*
chemical_list: C496789:9-fluorenylmethoxycarbonyl; D005449:Fluorenes; D014364:Tryptophan; D004122:Dimethylallyltranstransferase