Submitted to: Eukaryotic Cell
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/24/2007
Publication Date: 7/1/2007
Citation: Brown, D.W., Butchko, R.A., Busman, M., Proctor, R. 2007. The Fusarium verticillioides FUM gene cluster encodes a Zn(II)2Cys6 protein that affects FUM gene expression and fumonisin production. Eukaryotic Cell. 6:1210-1218. Interpretive Summary: Fusarium verticillioides is a common filamentous fungus that can cause a variety of diseases of corn. In addition, it can synthesize fumonisins, a family of toxins that may contaminate corn or corn products and are linked to numerous animal diseases including cancer and neural tube defects in humans. We are studying the biosynthesis of fumonisins by F. verticillioides because we believe that a thorough understanding of this process will lead to new strategies to limit mycotoxin contamination. In this study, we describe a new fumonisin gene, designated FUM21, and its initial characterization as a pathway specific transcriptional regulator that is absolutely required for fumonisin biosynthesis. We also provide additional evidence that alternative splice forms (ASFs) play a role in fumonisin biosynthesis. And finally, we suggest a model by which FUM21 ASF may regulate fumonisin biosynthesis. Understanding how fumonisin biosynthesis is regulated could benefit farmers and consumers by enabling the future development of new strategies to limit fumonisin contamination of corn and corn products.
Technical Abstract: Fumonisins are mycotoxins produced by some Fusarium species and can contaminate maize or maize products. Ingestion of fumonisins is associated with diseases, including cancer and neural tube defects, in humans and animals. In fungi, genes involved in synthesis of mycotoxins and other secondary metabolites are often located adjacent to each other in gene clusters. Such genes can encode structural enzymes, regulatory proteins, and/or proteins that provide self-protection. The fumonisin biosynthetic gene cluster includes 16 genes, none of which appear to play a role in regulation. In this study, we identified a previously undescribed gene (FUM21) located adjacent to the fumonisin polyketide synthase gene, FUM1. The presence of a Zn(II)2Cys6 DNA binding domain in the predicted protein suggested that it was involved in transcriptional regulation. FUM21 deletion mutants (deltafum21) produce little to no fumonisin in cracked maize cultures but some FUM1 and FUM8 transcripts in a liquid GYAM medium. Complementation of the deltafum21 mutant with the wild-type copy of the gene restored fumonisin production. Analysis of FUM21 transcripts identified four alternative splice forms (ASFs). Microarray analysis indicated differential expression of the FUM21 ASFs. We present a hypothetical model for a role of how FUM21 ASFs regulate fumonisin biosynthesis.