Effects of aflastatin A, an inhibitor of aflatoxin production, on aflatoxin biosynthetic pathway and glucose metabolism in Aspergillus parasiticus.
Aflastatin A inhibits aflatoxin production by Aspergillus parasiticus via an unknown mechanism. We found that aflastatin A clearly inhibited production of norsolorinic acid, an early biosynthetic intermediate of aflatoxin, at a concentration of 0.25 microg/ml. Reverse-transcriptase polymerase chain reaction (RT-PCR), and real-time quantitative PCR (TaqMan PCR) experiments indicated that the transcription of genes encoding aflatoxin biosynthetic enzymes (pksA, ver-1, and omtA) and a gene encoding a regulatory protein for expression of the biosynthetic enzymes (aflR) were significantly reduced by the addition of aflastatin A. We also found that aflastatin A elevated the glucose consumption and ethanol accumulation by A. parasiticus, and repressed transcription of genes involved in ethanol utilization. These results suggest that aflastatin A inhibits a very early step in aflatoxin biosynthesis prior to the transcription of aflR and can influence glucose metabolism in the fungus.
Kondo
T
T
Department of Applied Biological Chemistry, The University of Tokyo, Japan.
Sakurada
M
M
Okamoto
S
S
Ono
M
M
Tsukigi
H
H
Suzuki
A
A
Nagasawa
H
H
Sakuda
S
S
D000348:Aflatoxins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D001230:Aspergillus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D000431:Ethanol / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D007700:Kinetics; D011760:Pyrrolidinones / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects
D000348:Aflatoxins; D011760:Pyrrolidinones; C105377:aflastatin A; D000431:Ethanol; D005947:Glucose