title: Precursor-directed biosynthesis of micacocidin derivatives with activity against Mycoplasma pneumoniae.
abstract: Micacocidin is a promising natural product for the treatment of Mycoplasma pneumoniae infections. In the biosynthesis of this antibiotic, a fatty acid-AMP ligase (FAAL) activates the starter unit hexanoic acid as acyl-adenylate and forwards it to an iteratively acting polyketide synthase. Biochemical analysis of the FAAL revealed an extended substrate tolerance, thereby opening the door for the modification of a micacocidin residue that is barely accessible via semisynthesis. A total of six new analogues were generated by precursor-directed biosynthesis in this study and profiled against M. pneumoniae.
authors.affiliation: Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, Adolf-Reichwein-Str. 23, D-07745 Jena, Germany. markus.nett@hki-jena.de.
authors.forename: Martin F
authors.initials: MF
authors.lastname: Kreutzer
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kage
authors.forename: Jennifer
authors.initials: J
authors.lastname: Herrmann
authors.forename: Julia
authors.initials: J
authors.lastname: Pauly
authors.forename: Ron
authors.initials: R
authors.lastname: Hermenau
authors.forename: Rolf
authors.initials: R
authors.lastname: Müller
authors.forename: Dirk
authors.initials: D
authors.lastname: Hoffmeister
authors.forename: Markus
authors.initials: M
authors.lastname: Nett
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009177:Mycoplasma pneumoniae / Q000187:drug effects*; D009942:Organometallic Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D001688:Biological Products; D009942:Organometallic Compounds