G-protein signalling mediates differential production of toxic secondary metabolites

Filamentous fungi elaborate a complex array of secondary metabolites, inclu ding antibiotics and mycotoxins. As many of these compounds pose significan t economic and health concerns, elucidation of the underlying cellular mech anisms that control their production is essential. Previous work revealed t hat synthesis of the carcinogenic mycotoxins sterigmatocystin (ST) and afla toxin (AF) in Aspergillus species is negatively controlled by FadA, the alp ha -subunit of a heterotrimeric G-protein. In sharp contrast, we show here that the dominant activating fadA allele, fadA(G42R), stimulates transcript ion of a gene from the A. nidulans penicillin (PN) gene cluster and elevate s penicillin production. Thus, FadA has opposite roles in regulating the bi osynthesis of a potent antibiotic (PN) and a lethal mycotoxin (ST) in A. ni dulans. Furthermore, expression of fadA(G42R) in Fusarium sporotrichioides increases trichothecene (TR) mycotoxin production and alters TR gene expres sion. Our findings reveal that a G-protein defines an important control poi nt for differential expression of fungal secondary metabolites within and a cross fungal genera. These data provide critical evidence suggesting that t argeting G-protein signal transduction pathways as a means of controlling o r preventing the production of a single mycotoxin could have serious undesi rable consequences with regard to the production of other secondary metabol ites.