Genome mining of a prenylated and immunosuppressive polyketide from pathogenic fungi.
Activation of the polycyclic polyketide prenyltransferase (pcPTase)-containing silent clusters in Aspergillus fumigatus and Neosartorya fischeri led to isolation of a new metabolite neosartoricin (3). The structure of 3 was solved by X-ray crystallography and NMR to be a prenylated anthracenone. 3 exhibits T-cell antiproliferative activity with an IC(50) of 3 μM, suggestive of a physiological role as an immunosuppressive agent.
Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, California 90066, United States.
Yit-Heng
YH
Chooi
Jinxu
J
Fang
Hong
H
Liu
Scott G
SG
Filler
Pin
P
Wang
Yi
Y
Tang
D000818:Animals; D001232:Aspergillus fumigatus / Q000737:chemistry / Q000201:enzymology / Q000235:genetics*; D018360:Crystallography, X-Ray; D004122:Dimethylallyltranstransferase / Q000378:metabolism; D005658:Fungi / Q000235:genetics / Q000378:metabolism; D016678:Genome; D006367:HeLa Cells; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008968:Molecular Conformation; D055326:Neosartorya / Q000235:genetics* / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D061065:Polyketides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D054876:Prenylation
D007166:Immunosuppressive Agents; D061065:Polyketides; D004122:Dimethylallyltranstransferase