Protein synthesis inhibitory activity in culture filtrates from new strains of Streptomyces isolated from Brazilian tropical soils S.A. Reis 1 , L.V. Costa 1 , E.D.C. Cavalcanti 2 , M. Giambiagi-deMarval 2 , L.T.A.S. Seme ˆdo 2 , R.R.R. Coelho 2 , N. Moussatche ´ 1 and C.R.A. Damaso 1 1 Laborat  orio de Biologia Molecular de Vı ´rus, Instituto de Biofı ´sica Carlos Chagas Filho, and 2 Instituto de Microbiologia Prof. Paulo de G  oes, CCS, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil 2003/0110: received 10 February 2003, revised 16 April 2003 and accepted 17 April 2003 ABSTRACT S.A. REIS, L.V. COSTA, E.D.C. CAVALCANTI, M. GIAMBIAGI-DEMARVAL, L.T.A.S. SEME ˆ DO, R.R.R. COELHO, N. MOUSSATCHE ´ AND C.R.A. DAMASO. 2003. Aims: To investigate the effect of the culture supernatants from three newly isolated Streptomyces strains, 221, 235 and 606 on eukaryotic cells. Methods and Results: Cell lines were treated with the culture filtrates and assayed for protein synthesis by metabolic labelling, followed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis. RNA synthesis was investigated by [5- 3 H]uridine incorporation. The three culture filtrates presented a strong inhibitory activity, reducing total protein synthesis of different eukaryotic cell lines by more than 85%. No effect on cellular RNA synthesis was detected. The culture filtrates did not affect the growth of the prokaryotic cells tested. Conclusions: These new Streptomyces strains, recently isolated from Brazilian tropical soils, produce molecule(s) with inhibitory activity specific to eukaryote protein synthesis. Significance and Impact of the Study: Streptomyces strains 221, 235 and 606, probably representing new species, might produce new bioactive compound(s), and can be used as valuable tools to study the protein synthesis pathway in eukaryotes. Keywords: actinomycetes, antimetabolic activity, biotechnology, eukaryotic translation, translation inhibitor. INTRODUCTION Streptomyces spp. are Gram-positive bacteria isolated from several types of soils, including tropical forest, mud, cerrado and cave soils. They provide a valuable reservoir of secondary metabolites and enzymes (Sanglier et al. 1993) and, collectively, strains of the genus Streptomyces are responsible for producing about 85% of known antibiotics (Okami and Hotta 1988). The number of novel secondary metabolites continues to increase in pharmacological and biological screenings, indicating that new producer strains and species of Streptomyces with great potential in biotech- nology exist in nature (Harvey 2000). In the screening for micro-organisms capable of producing bioactive compounds, the exploration of new soils and habitats has been recom- mended (Nolan and Cross 1988). In this context, Brazilian tropical soils are an extremely rich source of biological compounds (Bull et al. 1992). Numerous antibiotics produced by distinct strains of Streptomyces induce the inhibition of protein synthesis. On some occasions, the primary target is the RNA metabolism, and the inhibition of cellular translation occurs as an indirect effect of the transcription shut-off. For example, strepto- lydigin, streptovaricin, adriamycin and daunorubicin inhibit the association of specific factors with the RNA polymerase II, being useful tools for examination of the transcription complex assembly process in eukaryotes (Logan et al. Correspondence to: C.R.A. Damaso, Instituto de Biofı ´ sica Carlos Chagas Filho- UFRJ Av. Brigadeiro Tromposvski, s/n, CCS, sala C1-028, Ilha do Fundao, Rio de Janeiro, RJ, 21941-590, Brazil (e-mail: damasoc@biof.ufrj.br). ª 2003 The Society for Applied Microbiology Letters in Applied Microbiology 2003, 37, 138–143