Inhibition of Ceramide Synthesis in Plants by Phytotoxins

Abstract

Inhibition of ceramide synthase has recently been identified (Abbas et al., 1993c, d; Abbas and Shier, 1997; Abbas et al., 1998c; Vesonder et al., 1992) as the mechanism of action of a small group of phytotoxins isolated from various fungi (Figure 1). This group of compounds causes dramatic effects in both animal and plant systems (Abbas et al., 1998a; Abbas and Boyette, 1992; Abbas et al., 1999; 1996; 1993b; 1995b, c, d;1991; Kellerman et al.,1990; Marasas et al., 1988; Shier et al., 1997; Shier and Abbas, 1999), and the evidence supports inhibition of ceramide synthase as the toxic mechanism (Abbas et al., 1995a; 1997b; 1994; Abbas and Shier, i 998; Norred,1993; Riley et al., 1994; 1996). Ceramide synthase is a key enzyme in the biosynthesis (Figure 2) of sphingolipid components of cell membranes (Figure 3) (Riley et al., 1993; Wang et al.,1991;1992; Lynch, 2000; Merrill, 1993b; Norred, 1993; Shier and Shier, 2000). Ceramide synthase inhibitors can be conveniently divided into two groups (Figure 1). The first group includes the AAL-toxins (Bottini and Gilchrist, 1981; Bottini et al., 1981; Caldas et al., 1994) and the fumonisins (Bezuidenhout et al., 1988; Gelderblom et al., 1988), both of which are structural analogs of the ceramide synthase substrate sphingosine. The second group consists of australifungin and its derivatives (Manadala et al., 1995), which are not apparent substrate analogs of ceramide synthase. These toxins were initially studied as inhibitors of mammalian ceramide synthase, but more recently studies have been extended to plant ceramide synthases. Research has been conducted to develop ceramide synthase as a target for new bioherbicides. However, fumonisins in food and feed have been shown to be toxic to animals and humans. The FDA has set guidelines for fumonisin levels in corn and corn products between 2 to 4 ppm. These mycotoxins are a serious public health issue (NTP, 1999). Thus, inhibitors of ceramide synthase have assumed importance in food safety, as well as in understanding the chemical ecology between plants and fungi.