Effects of Aflastatin A, an Inhibitor of Aflatoxin Production, on Aflatoxin Biosynthetic Pathway and Glucose Metabolism in Aspergillus parasiticus

• Published in: Journal of antibiotics Vol. 54; no. 8; pp. 650 - 657
• Main Authors: KONDO, TATSUHIKO, SAKURADA, MASARU, OKAMOTO, SUSUMU, ONO, MAKOTO, TSUKIGI, HIROSHI, SUZUKI, AKINORI, NAGASAWA, HIROMICHI, SAKUDA, SHOHEI
• Format: Journal Article
• Language: English
• Published: Tokyo JAPAN ANTIBIOTICS RESEARCH ASSOCIATION 2001; Japan Antibiotics Research Association
• Subjects: Aflatoxins - antagonists & inhibitors; Aflatoxins - biosynthesis; Aflatoxins - genetics; Aspergillus - drug effects; Aspergillus - genetics; Aspergillus - metabolism; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Ethanol - metabolism; Foods and miscellaneous; Glucose - metabolism; Kinetics; Medical sciences; Pyrrolidinones - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; Transcription, Genetic - drug effects; Tumors; Ethanol; Transcription; Glucose; Anticarcinogen; Metabolism; In vitro; Fungi; Toxin; Aspergillus parasiticus; Carcinogen; Microorganism culture; Fungi Imperfecti; Aflatoxin; Thallophyta
• ISSN: 0021-8820; 1881-1469
• DOI: 10.7164/antibiotics.54.650

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 μg/ml. Reversetranscriptase 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.