Aflatoxin biosynthesis is a novel source of reactive oxygen species—a potential redox signal to initiate resistance to oxidative stress?

Ludmila V. Roze, Maris Laivenieks, Sung Yong Hong, Josephine Wee, Shu Shyan Wong, Benjamin Vanos, Deena Awad, Kenneth C. Ehrlich, John E. Linz

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Aflatoxin biosynthesis in the filamentous fungus Aspergillus parasiticus involves a minimum of 21 enzymes, encoded by genes located in a 70 kb gene cluster. For aflatoxin biosynthesis to be completed, the required enzymes must be transported to specialized early and late endosomes called aflatoxisomes. Of particular significance, seven aflatoxin biosynthetic enzymes are P450/monooxygenases which catalyze reactions that can produce reactive oxygen species (ROS) as byproducts. Thus, oxidative reactions in the aflatoxin biosynthetic pathway could potentially be an additional source of intracellular ROS. The present work explores the hypothesis that the aflatoxin biosynthetic pathway generates ROS (designated as “secondary” ROS) in endosomes and that secondary ROS possess a signaling function. We used specific dyes that stain ROS in live cells and demonstrated that intracellular ROS levels correlate with the levels of aflatoxin synthesized. Moreover, feeding protoplasts with precursors of aflatoxin resulted in the increase in ROS generation. These data support the hypothesis. Our findings also suggest that secondary ROS may fulfill, at least in part, an important mechanistic role in increased tolerance to oxidative stress in germinating spores (seven-hour germlings) and in regulation of fungal development.

Original languageEnglish (US)
Pages (from-to)1411-1430
Number of pages20
JournalToxins
Volume7
Issue number5
DOIs
StatePublished - Apr 28 2015

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Health, Toxicology and Mutagenesis

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    Roze, L. V., Laivenieks, M., Hong, S. Y., Wee, J., Wong, S. S., Vanos, B., Awad, D., Ehrlich, K. C., & Linz, J. E. (2015). Aflatoxin biosynthesis is a novel source of reactive oxygen species—a potential redox signal to initiate resistance to oxidative stress? Toxins, 7(5), 1411-1430. https://doi.org/10.3390/toxins7051411