ABSTRACT: The Streptomyces lividans lsp gene encodes a type II signal peptidase (Lsp) that cleaves the type II leader peptides of lipoproteins. Transcriptional profiling of the bacterium depleted of the lsp gene mainly resulted in deactivation of the sigma U regulon, as well as in downregulation of genes involved in the biogenesis and function of ribosomes and genes encoding some major secretory proteins as determined by hybridisation of commercially available S. lividans genome-wide microarrays. Almost 50% of the dowregulated genes have been described as forming part of the stringent response in streptomycetes. The gene encoding the S. lividans extracellular foldase, the lipoprotein FkpA, is equally downregulated. Therefore, the deletion of lsp from the S. livdans genome temporarily triggers a cellular stress where the stringent response is, at least, partially induced. All microarray analyses were performed with RNA samples obtained from three independent cultures grown under identical conditions. The cDNA obtained from each RNA preparation of the Lsp-deficient strain was hybridised with the cDNA obtained from the equivalent RNA preparation of the wild type strain (S. lividans TK21).