Metabolic Labeling and Visualization of Isoprenoids Using Alkyne-Modified DMAPP Analogs in Bacillus subtilis.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος:	Metabolic Labeling and Visualization of Isoprenoids Using Alkyne-Modified DMAPP Analogs in Bacillus subtilis.
Συγγραφείς:	Hulsey ZN; Department of Chemistry, University of Tennessee, Knoxville, USA., McBee DP; Department of Chemistry, University of Tennessee, Knoxville, USA., Dolan CL; Department of Chemistry, University of Tennessee, Knoxville, USA., Rossi FM; Department of Chemistry, SUNY Cortland Cortland, New York, USA., Truslow NA; Department of Chemistry, University of Tennessee, Knoxville, USA., Taylor AR; Department of Chemistry, University of Tennessee, Knoxville, USA., Trybala TN; Department of Chemistry, University of Tennessee, Knoxville, USA., Baccile JA; Department of Chemistry, University of Tennessee, Knoxville, USA.
Πηγή:	Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2026 Aug 24; Vol. 65 (35), pp. e1590156. Date of Electronic Publication: 2026 Jul 10.
Τύπος έκδοσης:	Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Γλώσσα:	English
Στοιχεία περιοδικού:	Publisher: Wiley-VCH Country of Publication: Germany NLM ID: 0370543 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1521-3773 (Electronic) Linking ISSN: 14337851 NLM ISO Abbreviation: Angew Chem Int Ed Engl Subsets: MEDLINE
Imprint Name(s):	Publication: <2004-> : Weinheim : Wiley-VCH Original Publication: Weinheim/Bergstr. : New York, : Verlag Chemie ; Academic Press, c1962-
Ιατρικοί όροι (MeSH):	Bacillus subtilis/metabolism , Bacillus subtilis/chemistry , Alkynes/chemistry , Alkynes/metabolism , Terpenes/metabolism , Terpenes/chemistry , Organophosphorus Compounds/chemistry , Organophosphorus Compounds/metabolism , Hemiterpenes/chemistry , Hemiterpenes/metabolism
Περίληψη:	Isoprenoids are a chemically and functionally diverse class of metabolites that underlie essential bacterial physiology including respiration and cell envelope biogenesis. Chemical interrogation of isoprenoid metabolism remains limited because the two central five-carbon (C5) precursors, isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) are highly polar and cell-impermeant, rendering exogenous addition of them or functional analogs intractable. Here, we report the development of cell-permeant alkynylated DMAPP precursors (1-3) that enable DMAPP-specific bioorthogonal labeling of isoprenoids in Bacillus subtilis. Growth rescue, toxicity profiling, and downstream incorporation analyses showed that alkyne geometry and substitution pattern strongly influence the metabolic suitability of DMAPP surrogates. We found that a directly substituted Z-alkynyl DMAPP analog was the only biosynthetically productive surrogate tested. Metabolic incorporation of this probe resulted in regiospecific labeling of membrane-embedded isoprenoids, including menaquinone-7 (MK-7), bactoprenol, and tetraprenyl-β-curcumene. Pathway inhibition and supplementation assays demonstrate that the labeling efficiency of DMAPP surrogates is governed by competition with endogenous DMAPP and IPP. Lastly, post-incorporation CuAAC derivatization enabled direct visualization of isoprenoid localization and targeted mass-spectrometric profiling of labeled prenyl metabolites. These results establish a general chemical platform for bioorthogonal tagging of C5 metabolism in B. subtilis. (© 2026 The Author(s). Angewandte Chemie International Edition published by Wiley‐VCH GmbH.)
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Grant Information:	1R35GM157211-01 United States NH NIH HHS; CHE-2204170 National Science Foundation; R35 GM157211 United States GM NIGMS NIH HHS; T32 GM142621 United States GM NIGMS NIH HHS; 1 T32 GM142621 United States NH NIH HHS
Contributed Indexing:	Keywords: Bacillus subtilis; biochemistry; biogenesis; bioorthogonal chemistry; chemistry; isopentenyl pyrophosphate; prenylation; pyrophosphate; terpenoid
Substance Nomenclature:	0 (Alkynes) 0 (Terpenes) 0 (Organophosphorus Compounds) 0 (Hemiterpenes) 358-72-5 (3,3-dimethylallyl pyrophosphate) 358-71-4 (isopentenyl pyrophosphate)
Entry Date(s):	Date Created: 20260710 Date Completed: 20260824 Latest Revision: 20260916
Update Code:	20260916
PubMed Central ID:	PMC13502626
DOI:	10.1002/anie.1590156
PMID:	42429022
Βάση Δεδομένων:	MEDLINE

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