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Proteomic signature of fatty acid biosynthesis inhibition available for in vivo mechanism-of-action studies

Academic Article
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Overview

authors

  • Wenzel, M.
  • Patra, M.
  • Albrecht, D.
  • Chen, D. Y. K.
  • Nicolaou, K.C.
  • Metzler-Nolte, N.
  • Bandow, J. E.

publication date

  • June 2011

journal

  • Antimicrobial Agents and Chemotherapy  Journal

abstract

  • Fatty acid biosynthesis is a promising novel antibiotic target. Two inhibitors of fatty acid biosynthesis, platencin and platensimycin, were recently discovered and their molecular targets identified. Numerous structure-activity relationship studies for both platencin and platensimycin are currently being undertaken. We established a proteomic signature for fatty acid biosynthesis inhibition in Bacillus subtilis using platencin, platensimycin, cerulenin, and triclosan. The induced proteins, FabHA, FabHB, FabF, FabI, PlsX, and PanB, are enzymes involved in fatty acid biosynthesis and thus linked directly to the target pathway. The proteomic signature can now be used to assess the in vivo mechanisms of action of compounds derived from structure-activity relationship programs, as demonstrated for the platensimycin-inspired chromium bioorganometallic PM47. It will further serve as a reference signature for structurally novel natural and synthetic antimicrobial compounds with unknown mechanisms of action. In summary, we described a proteomic signature in B. subtilis consisting of six upregulated proteins that is diagnostic of fatty acid biosynthesis inhibition and thus can be applied to advance antibacterial drug discovery programs.

subject areas

  • Adamantane
  • Aminobenzoates
  • Aminophenols
  • Anilides
  • Anti-Bacterial Agents
  • Bacillus subtilis
  • Bacterial Proteins
  • Drug Discovery
  • Fatty Acids
  • Polycyclic Compounds
  • Proteomics
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Identity

PubMed Central ID

  • PMC3101464

International Standard Serial Number (ISSN)

  • 0066-4804

Digital Object Identifier (DOI)

  • 10.1128/aac.00078-11

PubMed ID

  • 21383089
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Additional Document Info

start page

  • 2590

end page

  • 2596

volume

  • 55

issue

  • 6

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