title: Polyketide Bioderivatization Using the Promiscuous Acyltransferase KirCII.
abstract: During polyketide biosynthesis, acyltransferases (ATs) are the essential gatekeepers which provide the assembly lines with precursors and thus contribute greatly to structural diversity. Previously, we demonstrated that the discrete AT KirCII from the kirromycin antibiotic pathway accesses nonmalonate extender units. Here, we exploit the promiscuity of KirCII to generate new kirromycins with allyl- and propargyl-side chains in vivo, the latter were utilized as educts for further modification by "click" chemistry.
authors.affiliation: Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark , Kemitorvet Building B220, 2800 Kgs. Lyngby, Denmark.|German Centre for Infection Research (DZIF), Partner site Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, Germany.|Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Mikrobiologie/Biotechnologie, Eberhard Karls Universität Tübingen , Auf der Morgenstelle 28, 72076 Tübingen, Germany.
authors.forename: Ewa M
authors.initials: EM
authors.lastname: Musiol-Kroll
authors.affiliation: Institut für Organische Chemie, Eberhard Karls Universität Tübingen , Auf der Morgenstelle 18, 72076 Tübingen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Zubeil
authors.affiliation: Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Mikrobiologie/Biotechnologie, Eberhard Karls Universität Tübingen , Auf der Morgenstelle 28, 72076 Tübingen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schafhauser
authors.affiliation: Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Mikrobiologie/Biotechnologie, Eberhard Karls Universität Tübingen , Auf der Morgenstelle 28, 72076 Tübingen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Härtner
authors.affiliation: Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Mikrobiologie/Biotechnologie, Eberhard Karls Universität Tübingen , Auf der Morgenstelle 28, 72076 Tübingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kulik
authors.affiliation: North Carolina State University , Department of Chemistry, Raleigh, North Carolina 27695-8204, United States.
authors.forename: John
authors.initials: J
authors.lastname: McArthur
authors.affiliation: North Carolina State University , Department of Chemistry, Raleigh, North Carolina 27695-8204, United States.
authors.forename: Irina
authors.initials: I
authors.lastname: Koryakina
authors.affiliation: German Centre for Infection Research (DZIF), Partner site Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, Germany.|Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Mikrobiologie/Biotechnologie, Eberhard Karls Universität Tübingen , Auf der Morgenstelle 28, 72076 Tübingen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wohlleben
authors.affiliation: Institut für Organische Chemie, Eberhard Karls Universität Tübingen , Auf der Morgenstelle 18, 72076 Tübingen, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Grond
authors.affiliation: North Carolina State University , Department of Chemistry, Raleigh, North Carolina 27695-8204, United States.
authors.forename: Gavin J
authors.identifier: 0000-0003-2172-9063
authors.initials: GJ
authors.lastname: Williams
authors.affiliation: Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark , Kemitorvet Building B220, 2800 Kgs. Lyngby, Denmark.|Department of Chemical and Biomolecular Engineering (BK21 Plus Program), Korea Advanced Institute of Science and Technology (KAIST) , 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea.
authors.forename: Sang Yup
authors.identifier: 0000-0003-0599-3091
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark , Kemitorvet Building B220, 2800 Kgs. Lyngby, Denmark.|German Centre for Infection Research (DZIF), Partner site Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, Germany.|Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Mikrobiologie/Biotechnologie, Eberhard Karls Universität Tübingen , Auf der Morgenstelle 28, 72076 Tübingen, Germany.
authors.forename: Tilmann
authors.identifier: 0000-0002-8260-5120
authors.initials: T
authors.lastname: Weber
mesh_terms: D000217:Acyltransferases / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000378:metabolism; D001419:Bacteria / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D048630:Polyketide Synthases / Q000378:metabolism; D061065:Polyketides / Q000378:metabolism*; D011728:Pyridones / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D061065:Polyketides; D011728:Pyridones; D048630:Polyketide Synthases; D000217:Acyltransferases; C008536:mocimycin
keywords: antibiotic; click chemistry; engineering; kirromycin; polyketide synthase; trans-acyltransferase