Solid‐Phase Enrichment and Analysis of Azide‐Labeled Natural Products: Fishing Downstream of Biochemical Pathways. Issue 2 (2nd December 2015)

• Record Type: Journal Article
• Authors: Pérez, Alexander J.; Wesche, Frank; Adihou, Hélène; Bode, Helge B.
• Is Part Of: Chemistry. Volume 22:Issue 2(2016)
• Page Start: 639
• Page End: 645
• Publication Date: 2015-12-02
• Subjects: azides -- click chemistry -- fatty acids -- metabolic labeling -- natural products; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201503781
• Languages: English
• ISSNs: 0947-6539

Abstract

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. Abstract : Elucidating biochemical pathways : Using a cleavable azide‐reactive resin (CARR), a new method for natural product discovery is presented. Various azidated precursors have been employed to track their metabolism in different bacterial strains, resulting in the simple "fishing" of known and novel natural products (see figure; TCEP=tris(2‐carboxyethyl)phosphine).