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Molecular & Cellular Proteomics 6:1248-1256, 2007.
© 2007 by The American Society for Biochemistry and Molecular Biology, Inc.

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Research

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

Overlapping Signaling Routes^*,S

Zsuzsanna Birkó, Sylwia Bialek, Krisztina Buzás^¶,||, Emília Szájli^¶, Bjørn A. Traag, Katalin F. Medzihradszky^¶,**, Sebastien Rigali, Erik Vijgenboom, András Penyige, Zoltán Kele, Gilles P. van Wezel^, and Sándor Biró^,¶¶

From the Department of Human Genetics, Faculty of Medicine, Medical and Health Science Center, University of Debrecen, Nagyerdei körút 98, H-4032 Debrecen, Hungary, Microbial Development, Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, P. O. Box 9502, 2300 RA Leiden, The Netherlands, ^¶ Proteomics Research Group, Biological Research Center, Hungarian Academy of Sciences, Temesvári körút 62, H-6726 Szeged, Hungary, ^|| Kromat Kft, Sirály utca 3, H-1124 Budapest, Hungary, ^** Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94143-0446, and Department of Medicinal Chemistry, Faculty of Medicine, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary

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.

^¶¶ To whom correspondence may be addressed. E-mail: sbiro{at}dote.hu

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