title: Solid-Phase Enrichment and Analysis of Azide-Labeled Natural Products: Fishing Downstream of Biochemical Pathways.
abstract: Many methods have been devised over the decades to trace precursors of specific molecules in cellular environments as, for example, in biosynthesis studies. The advent of click chemistry has facilitated the powerful combination of tracing and at the same time sieving the highly complex metabolome for compounds derived from simple or complex starting materials, especially when the click reaction takes place on a solid support. While the principle of solid-phase click reactions has already been successfully applied for selective protein and peptide enrichment, the successful enrichment of much smaller primary and secondary metabolites, showing great structural diversity and undergoing many different biosynthetic steps, has seen only little development. For bacterial secondary metabolism, a far broader tolerance for "clickable" precursors was observed than in ribosomal proteinogenesis, thus making this method a surprisingly valuable tool for the tracking and discovery of compounds within the cellular biochemical network. The implementation of this method has led to the identification of several new compounds from the bacterial genera Photorhabdus and Xenorhabdus, clearly proving its power.
authors.affiliation: Merck Stiftungsprofessur für Molekulare Biotechnologie, Fachbereich Biowissenschaften, Goethe Universität Frankfurt, Max-von-Laue-Strasse 9, 60438 Frankfurt (Germany).
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Pérez
authors.affiliation: Merck Stiftungsprofessur für Molekulare Biotechnologie, Fachbereich Biowissenschaften, Goethe Universität Frankfurt, Max-von-Laue-Strasse 9, 60438 Frankfurt (Germany).
authors.forename: Frank
authors.initials: F
authors.lastname: Wesche
authors.affiliation: Merck Stiftungsprofessur für Molekulare Biotechnologie, Fachbereich Biowissenschaften, Goethe Universität Frankfurt, Max-von-Laue-Strasse 9, 60438 Frankfurt (Germany).
authors.forename: Hélène
authors.initials: H
authors.lastname: Adihou
authors.affiliation: Merck Stiftungsprofessur für Molekulare Biotechnologie, Fachbereich Biowissenschaften, Goethe Universität Frankfurt, Max-von-Laue-Strasse 9, 60438 Frankfurt (Germany).|Buchmann Institute for Molecular Life Sciences (BMLS), Goethe Universität Frankfurt, Max-von-Laue-Strasse 15, 60438 Frankfurt (Germany).
authors.forename: Helge B
authors.initials: HB
authors.lastname: Bode
mesh_terms: D000818:Animals; D001386:Azides / Q000138:chemical synthesis* / Q000737:chemistry; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D057930:Click Chemistry; D005227:Fatty Acids / Q000737:chemistry* / Q000378:metabolism; D005399:Fishes; D020637:Photorhabdus / Q000737:chemistry; D060327:Solid-Phase Synthesis Techniques / Q000379:methods*; D020593:Xenorhabdus / Q000737:chemistry
chemical_list: D001386:Azides; D001688:Biological Products; D005227:Fatty Acids
keywords: azides; click chemistry; fatty acids; metabolic labeling; natural products