A single target is sufficient to account for the biological effects of the A-factor receptor protein of Streptomyces griseus.
In the model of the A-factor (2-isocapryloyl-3R-hydroxymethyl-gamma-butyrolactone) regulatory cascade in Streptomyces griseus, A-factor binds ArpA, the A-factor receptor protein, that has bound to the adpA promoter and dissociates it from the DNA, thus inducing the transcription of adpA. AdpA switches on the transcription of a number of genes required for secondary metabolism and morphological differentiation, forming an AdpA regulon. Consistent with this model, arpA null mutants produced streptomycin and a yellow pigment in larger amounts and formed aerial hyphae from an earlier growth stage than the wild-type strain. On the other hand, mutant MK2, expressing a mutant ArpA (Trp119Ala), neither produced secondary metabolites nor formed aerial hyphae, because this A-factor-insensitive mutant ArpA always bound to and repressed the adpA promoter due to the amino acid replacement of Trp-119 with Ala. Introduction of adpA under the control of a foreign promoter into mutant MK2 restored all of the phenotypes that we could observe, which suggests that the only significant target of ArpA is adpA. In contrast to other gamma-butyrolactone regulatory systems, disruption of arpA had no effect on A-factor production, indicating that ArpA does not regulate A-factor biosynthesis. Instead, A-factor production was found to be repressed by AdpA in a two-step regulatory feedback loop.
Kato
Jun-ya
JY
Department of Biotechnology, Graduate School of Agriculture and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
Miyahisa
Ikuo
I
Mashiko
Mari
M
Ohnishi
Yasuo
Y
Horinouchi
Sueharu
S
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000096:biosynthesis* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003470:Culture Media; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D009154:Mutation; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013305:Streptomyces griseus / Q000254:growth & development / Q000378:metabolism*; D013307:Streptomycin / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
C401645:AdpA protein, Streptomyces griseus; D001426:Bacterial Proteins; D003470:Culture Media; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; C025035:A-factor (Streptomyces); D015107:4-Butyrolactone; D013307:Streptomycin