Gene replacement analysis of the butyrolactone autoregulator receptor (FarA) reveals that FarA acts as a novel regulator in secondary metabolism of Streptomyces lavendulae FRI-5

'IM-2 [(2R,3R,1'R)-2-1'-hydroxybutyl-3-hydroxymethyl gamma -butanolide] is a gamma -butyrolactone autoregulator which, in Streptomyces lavendulae FRI- 5, switches off the production of D-cycloserine but switches on the product ion of a blue pigment and several nucleoside antibiotics. To clarify the in vivo function of an IM-2-specific receptor (FarA) in the IM-2 signaling ca scade of S. lavendulae FRI-5, a farA deletion mutant was constructed by mea ns of homologous recombination. On several solid media, no significant diff erence in morphology was observed between the wild-type strain and the farA mutant (strain K104), which demonstrated that the IM-2-FarA system does no t participate in the morphological control of S. lavendulae FRI-5. In liqui d media, the farA mutant overproduced nucleoside antibiotics and produced b lue pigment earlier than did the wild-type strain, suggesting that the FarA protein acts primarily as a negative regulator on the biosynthesis of thes e compounds in the absence of IM-2. However, contrary to the IM-2-dependent suppression of D-cycloserine production in the wild-type strain, overprodu ction of D-cycloserine was observed in the farA mutant, indicating for the first time that the presence of both IM-2 and intact FarA are necessary for the suppression of D-cycloserine biosynthesis.