The Secreted Signaling Protein Factor C Triggers the A-factor Response Regulon in Streptomyces griseus

Abstract

Members of the prokaryotic genus Streptomyces produce over 60% of all known antibiotics and a wide range of industrial enzymes. A leading theme in microbiology is which signals are received and transmitted by these organisms to trigger the onset of morphological differentiation and antibiotic production. The small ␥-butyrolactone A-factor is an important autoregulatory signaling molecule in streptomycetes, and A-factor mutants are blocked in development and antibiotic production. In this study we showed that heterologous expression of the 324-amino acid secreted regulatory protein Factor C resulted in restoration of development and enhanced antibiotic production of an A-factor-deficient bald mutant of Streptomyces griseus, although the parental strain lacks an facC gene. Proteome analysis showed that in the facC transformant the production of several secreted proteins that belong to the A-factor regulon was restored. HPLC-MS/MS analysis indicated that this was due to restoration of A-factor production to wild-type levels in the transformant. This indicates a connection between two highly divergent types of signaling molecules and possible interplay between their regulatory networks.

Novel and sensitive qPCR assays for the detection and identification of aspergillosis causing species

“…showed that it compensates for a mutation that led to almost complete abolishment of production of A factor and regulates the production of many sporulation specific proteins [22,23].…”

Streptomyces griseus 45H, a producer of the extracellular autoregulator protein factor C, is a member of the species Streptomyces albidoflavus

“…The identity and mode of action of factor C, the morphological differentiation of S. griseus 45H and the effect of factor C on the differentiation of S. griseus 52-1 have been the subject of many publications (for a complete list see http://web.dote.hu/~sbiro/). Interaction between factor C and the regulon of S. griseus controlled by the best known c-butyrolactone autoregulator, A-factor (Ohnishi et al, 2005), has been described recently (Birkó et al, 2007).Since the two S. griseus strains (52-1 and 45H) differed in several substantial properties (Table 1), the origin of S. griseus 45H has often been questioned (Fehér & Szabó , 1978). Unquestionable evidence that the strain S. griseus 45H could not be a descendant of S. griseus 52-1 was obtained when the cloned factor C gene (facC) did not hybridize to the genomic DNA of S. griseus 52-1 (Birkó et al., 1999).…”

“…The identity and mode of action of factor C, the morphological differentiation of S. griseus 45H and the effect of factor C on the differentiation of S. griseus 52-1 have been the subject of many publications (for a complete list see http://web.dote.hu/~sbiro/). Interaction between factor C and the regulon of S. griseus controlled by the best known c-butyrolactone autoregulator, A-factor (Ohnishi et al, 2005), has been described recently (Birkó et al, 2007).…”

Lack of A-factor Production Induces the Expression of Nutrient Scavenging and Stress-related Proteins in Streptomyces griseus>

“…Our previous results (14) indicate a connection between two highly divergent types of signaling molecules and possible interplay between their regulatory networks. In preliminary experiments we observed characteristic differences between the extracellular proteomes of the strains that prompted detailed further analysis facilitated by the currently available DNA sequence of the genome of S. griseus IFO 13350 (17).…”