Direct Interaction of Chivosazole F with Actin Elicits Cell Responses Similar to Latrunculin A but Distinct from Chondramide

ACS Chem Biol. 2017 Sep 15;12(9):2264-2269. doi: 10.1021/acschembio.7b00385. Epub 2017 Aug 15.


The microbial metabolite Chivosazole F has been described to affect the cytoskeleton and to inhibit actin polymerization in vitro. Applying orthogonal genomic and proteomics approaches, we now show for the first time that Chivosazole F exerts its effect by directly interacting with actin and demonstrate the cellular impact of Chivosazole F in an unbiased, genome-wide context in yeast and in mammalian cells. Furthermore, mutation-based resistance mapping identifies two SNPs located in the putative Chivosazole F binding site of actin. Comparing chemogenomic profiles and responses to the Chivosazole F-resistant SNPs shows a partially conserved mechanism of action for Chivosazole F and Latrunculin A, but clear divergence from Chondramide. In addition, C14orf80 is an evolutionarily highly conserved ORF, lacking any functional annotation. As editing of C14orf80 leads to Chivosazole F hyper-resistance, we propose a function for this gene product in counteracting perturbation of actin filaments.

MeSH terms

  • Actin Cytoskeleton / drug effects
  • Actin Cytoskeleton / genetics
  • Actin Cytoskeleton / metabolism
  • Actins / genetics
  • Actins / metabolism*
  • Binding Sites
  • Bridged Bicyclo Compounds, Heterocyclic / chemistry
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
  • Depsipeptides / chemistry
  • Depsipeptides / pharmacology*
  • HEK293 Cells
  • Humans
  • Macrolides / chemistry
  • Macrolides / pharmacology*
  • Mutation
  • Myxococcales / chemistry
  • Thiazolidines / chemistry
  • Thiazolidines / pharmacology*


  • Actins
  • Bridged Bicyclo Compounds, Heterocyclic
  • Depsipeptides
  • Macrolides
  • Thiazolidines
  • chivosazole F
  • chondramide A
  • latrunculin A