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 paper we show that the 324 aa secreted heterologous protein, Factor C results in restoration of development and enhanced antibiotic production of an A-factor deficient strain of Streptomyces griseus by eliciting a very similar response, even though the parental strain lacks a 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. This indicates a connection between two highly divergent types of signaling molecules and possible interplay between their regulatory networks.