The p-lactam antibiotic penicillin is produced as end product by only
some filamentous fungi, most notably by Aspergillus nidulans and Penic
illium chrysogenum. The biosynthesis of this secondary metabolite is c
atalyzed by three enzymes which are encoded by the following three gen
es: acvA (pcbAB), ipnA (pcbC) and aat (penDE). The genes are organized
into a gene cluster. In A. nidulans, several studies have indicated t
hat the genes are controlled by a complex regulatory network. The wide
-domain regulatory protein PACC binds to the intergenic region between
acvA and ipnA and, at alkaline pH, increases at least ipnA gene trans
cription. An additional DNA binding protein (PENR1) was suggested to r
epress acvA and to activate ipnA and aat expression. Furthermore, thre
e recessive trans-acting mutations have been characterized (prgAl, prg
Bl, npeEl) which most likely correspond to positively acting regulator
y genes of the penicillin biosynthesis genes.