Andrastin A and barceloneic acid metabolites, protein farnesyl transferase inhibitors from Penicillium albocoremium: chemotaxonomic significance and pathological implications.
A survey of Penicillium albocoremium was undertaken to identify potential taxonomic metabolite markers. One major and four minor metabolites were consistently produced by the 19 strains surveyed on three different media. Following purification and spectral studies, the metabolites were identified as the known protein farnesyl transferase inhibitors andrastin A (1) and barceloneic acid A (2) along with barceloneic acid B (3), barceloneic lactone (4), and methyl barceloneate (5). These compounds are significant taxonomic markers for P. albocoremium; moreover this is the first report of a methyl ester of a barceloneic acid being produced as a secondary metabolite. Tissue extracts created following pathogenicity trials involving P. albocoremium and Allium cepa confirmed the production of these five metabolites in planta. Barceloneic acid B was found to be biologically active against a P388 murine leukemia cell line.
Overy
David P
DP
Centre for Microbial Biotechnology, Biocentrum-DTU, Technical University of Denmark, Kgs Lyngby, Denmark. do@biocentrum.dtu.dk
Larsen
Thomas O
TO
Dalsgaard
Petur W
PW
Frydenvang
Karla
K
Phipps
Richard
R
Munro
Murray H G
MH
Christophersen
Carsten
C
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000730:Androstadienes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D051379:Mice; D019906:Nuclear Magnetic Resonance, Biomolecular; D019697:Onions / Q000382:microbiology*; D010407:Penicillium / Q000378:metabolism*; D010647:Phenyl Ethers / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D012459:Salicylates / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization
D000730:Androstadienes; D004791:Enzyme Inhibitors; D010647:Phenyl Ethers; D012459:Salicylates; C100395:andrastin A; C095779:barceloneic acid A; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase