In the A-factor regulatory cascade leading to the onset of streptomycin bio
synthesis and aerial mycelium formation in Streptomyces griseus, the A-fact
or receptor protein (ArpA) serves as a DNA-binding repressor and A-factor r
eleases the repression by binding to ArpA and dissociating it from the DNA.
Mutants defective in arpA therefore produce streptomycin and aerial hyphae
in the absence of A-factor. A gene that inhibits streptomycin production a
nd aerial hyphae formation in an arpA mutant was cloned on a high-copy-numb
er plasmid and found to encode a eukaryotic-type adenylate cyclase (CyaA).
Consistent with this, an exogenous supply of cAMP at high concentration alm
ost abolished streptomycin production and aerial hyphae formation. On the o
ther hand, cAMP at lower concentrations stimulated or accelerated these dev
elopmental processes. The effects of cAMP were detectable only in arpA muta
nts, nd not in the wild-type strain; an exogenous supply of cAMP or cyaA di
sruption in the wild-type strain caused almost no effect on these phenotype
s. Thus the effects of cAMP became apparent only in the arpA-defective back
ground. cAMP at high concentrations inhibited stringent response factor ppG
pp production, which is important for the onset of antibiotic biosynthesis.
cAMP also influenced the timing of tyrosine phosphorylation of more than n
ine proteins. These findings show that a cAMP regulatory relay for physiolo
gical and morphological development functions in a concerted and interdepen
dent way with other signal transduction pathways.