Conserved Regulatory Mechanisms Controlling Aflatoxin and Sterigmatocystin Biosynthesis

Abstract

Filamentous fungi produce a wide array of compounds known as secondary metabolites or natural products (i.e. Adrio and Demain, 2003; Reverberi et al 2010; Brakhage and Schroeckh 2011). The exact function of these compounds is unknown but it is postulated that they provide fungi with an advantage in their ecological niche (Keller et al., 2005; Georgianna and Payne 2009). The broad group of natural products includes compounds such as antibiotics, pigments and also mycotoxins (Fig.1). Among mycotoxins, aflatoxins (AF), specifically AF B1, are the most potent carcinogenic natural compounds known, and they are mainly produced by the opportunistic plant pathogens Aspergillus flavus and Aspergillus parasiticus (Squire 1989; Sweeny and Dobson 1999; Payne and Brown, 1998). Other AFproducers among Aspergilli include Aspergillus nomius, Aspergillus ochraceoroseus, Aspergillus bombycis and Aspergillus pseudotamari (Cary and Ehrlich, 2006). Aspergillus flavus and Aspergillus parasiticus have the ability to colonize oil seed crops of agricultural importance, such as corn, cotton, peanuts, sorghum and tree nuts. Ingestion of aflatoxin contaminated food can cause hepatocellular carcinoma, immunotoxicity, and teratogenic effects (Dvorackova and Kusak, 1990; Trail et al., 1995; Wogan et al., 1992). Various developed countries have strict regulation on the amount of AF allowed in food commodities. Contaminated crops above the permitted limit have to be destroyed, resulting in economic losses. The annual estimated loss due to AF contamination is attributed at approximately $270 million in the USA alone (Richard and Payne, 2003). It is known that AF and a related mycotoxin called sterigmatocystin (ST) (Fig.2) are synthesized through the same conserved biosynthetic pathway, in which ST is the penultimate precursor. ST is produced by several Aspergillus species, including Aspergillus nidulans, one of the most characterized eukaryotic systems that has been used as a model organism for more than 60 years (Pontecorvo et al., 1953). The elevated number of characterized A. nidulans genes and mutant strains makes this model fungus ideal for genetic and molecular studies. There is a physical and genetic map of the eight chromosomes in A. nidulans. The whole A. nidulans genome has been sequenced and annotated, and has been compared with other Aspergillus genomes (David et al., 2008; Galagan et al., 2005). Structural and signaling pathway genes controlling ST production in A. nidulans are also found in AF-producer Aspergillus spp. (Hicks et al., 1997; reviewed by