Introduction of a leptomycin-sensitive mutation into Fusarium graminearum

Abstract

LMB is a secondary metabolite of a strain of Streptomyces. The binding of LMB to chromosomal region maintenance 1 protein (CRM1) abolishes the association of this exportin with the nuclear export signal, and inhibits nuclear export of proteins in eukaryotes1),2). In an LMB-sensitive fission yeast, Schizosacchromyces pombe, a single amino acid exchange of Cys-529 to Ser in the central conserved region of CRM1 (Fig. 1A) confers a high resistance to LMB, suggesting that the Cys529 residue is critical for LMB binding3). Unlike higher eukaryotes and S. pombe, Saccharomyces cerevisiae and Aspergillus nidulans are highly resistant to LMB. In their CRM1 orthologues, a Cys residue essential for LMB binding is substituted for a Thr residue (Fig. 1A). Sequence analysis of the F. graminearum CRM1 orthologue (hereafter referred to as FgCrm1) (FGSG_10894) indicates that FgCRM1 contains an LMB-insensitive Thr residue (Fig. 1A). Indeed, most fungi appear to be resistant to LMB because the Cys residue is similarly substituted for a Thr residue in their orthologues.