Tremorgenic mycotoxin intoxication with penitrem A and roquefortine in two dogs

ABSTRACT Aflatrem is a potent tremorgenic mycotoxin produced by the soil fungus Aspergillus flavus and is a member of a large structurally diverse group of secondary metabolites known as indole-diterpenes. By using degenerate primers for conserved domains of fungal geranylgeranyl diphosphate synthases, we cloned two genes, atmG and ggsA (an apparent pseudogene), from A. flavus. Adjacent to atmG are two other genes, atmC and atmM. These three genes have 64 to 70% amino acid sequence similarity and conserved synteny with a cluster of orthologous genes, paxG, paxC, and paxM, from Penicillium paxilli which are required for indole-diterpene biosynthesis. atmG, atmC, and atmM are coordinately expressed, with transcript levels dramatically increasing at the onset of aflatrem biosynthesis. A genomic copy of atmM can complement a paxM deletion mutant of P. paxilli, demonstrating that atmM is a functional homolog of paxM. Thus, atmG, atmC, and atmM are necessary, but not sufficient, for aflatrem biosynthesis by A. flavus. This provides the first genetic evidence for the biosynthetic pathway of aflatrem in A. flavus.

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Aflatrem, the tremorgenic mycotoxin from aspergillus flavus

Mycopathologia ◽

10.1007/bf00683969 ◽

1979 ◽

Vol 66 (3) ◽

pp. 183-185 ◽

Cited By ~ 32

Author(s):

Rex T. Gallagher ◽

Benjamin J. Wilson

Keyword(s):

Aspergillus Flavus ◽

Tremorgenic Mycotoxin

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Pharmacological Effects of the Tremorgenic Mycotoxin Fumitremorgin A

The Japanese Journal of Pharmacology ◽

10.1254/jjp.40.481 ◽

1986 ◽

Vol 40 (4) ◽

pp. 481-489 ◽

Cited By ~ 7

Author(s):

Mariko NISHIYAMA ◽

Tetsuro KUGA

Keyword(s):

Pharmacological Effects ◽

Tremorgenic Mycotoxin

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ChemInform Abstract: Fungal Products. Part 21. Isolation and Structures of Indoloditerpenes, Possible Biosynthetic Intermediates to the Tremorgenic Mycotoxin, Paxilline, from Emericella striata.

ChemInform ◽

10.1002/chin.198852306 ◽

1988 ◽

Vol 19 (52) ◽

Author(s):

K. NOZAWA ◽

S. NAKAJIMA ◽

K. KAWAI ◽

S. UDAGAWA

Keyword(s):

Tremorgenic Mycotoxin

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Territrem B, a Tremorgenic Mycotoxin That Inhibits Acetylcholinesterase with a Noncovalent yet Irreversible Binding Mechanism

Journal of Biological Chemistry ◽

10.1074/jbc.274.49.34916 ◽

1999 ◽

Vol 274 (49) ◽

pp. 34916-34923 ◽

Cited By ~ 29

Author(s):

Jen-Wei Chen ◽

Ying-Ling Luo ◽

Ming-Jing Hwang ◽

Fu-Chuo Peng ◽

Kuo-Huang Ling

Keyword(s):

Binding Mechanism ◽

Irreversible Binding ◽

Tremorgenic Mycotoxin

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Tremorgenic Encephalopathy: A Role of Mycotoxins in the Production of CNS Disease in Humans?

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100048010 ◽

1993 ◽

Vol 20 (3) ◽

pp. 237-239 ◽

Cited By ~ 39

Author(s):

K.E. Gordon ◽

R.E. Masotti ◽

W.R. Waddell

Keyword(s):

Inhalation Exposure ◽

Definitive Diagnosis ◽

Neurological Syndrome ◽

Cns Disease ◽

Tremorgenic Mycotoxin

ABSTRACT:We describe a young man who, shortly after exposure to moldy silage, developed a neurological syndrome consisting of dementia and a remarkable tremor which was precipitated by movement. All symptoms resolved within one week. Despite investigation, no definitive diagnosis was reached. We propose that this patient's illness may have resulted from inhalation exposure to a tremorgenic mycotoxin.

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