The Level of AdpA Directly Affects Expression of Developmental Genes in Streptomyces coelicolor

Abstract

AdpA is a key regulator of morphological differentiation in Streptomyces. In contrast to Streptomyces griseus, relatively little is known about AdpA protein functions in Streptomyces coelicolor. Here, we report for the first time the translation accumulation profile of the S. coelicolor adpA (adpA Sc ) gene; the level of S. coelicolor AdpA (AdpA Sc ) increased, reaching a maximum in the early stage of aerial mycelium formation (after 36 h), and remained relatively stable for the next several hours (48 to 60 h), and then the signal intensity decreased considerably. AdpA Sc specifically binds the adpA Sc promoter region in vitro and in vivo, suggesting that its expression is autoregulated; surprisingly, in contrast to S. griseus, the protein presumably acts as a transcriptional activator. We also demonstrate a direct influence of AdpA Sc on the expression of several genes whose products play key roles in the differentiation of S. coelicolor: STI, a protease inhibitor; RamR, an atypical response regulator that itself activates expression of the genes for a small modified peptide that is required for aerial growth; and ClpP1, an ATP-dependent protease. The diverse influence of AdpA Sc protein on the expression of the analyzed genes presumably results mainly from different affinities of AdpA Sc protein to individual promoters.Streptomycetes, GC-rich Gram-positive soil bacteria known for their ability to produce many valuable antibiotics and other secondary metabolites, undergo complex morphological differentiation (4, 10). The genome of the model species Streptomyces coelicolor A3(2) was the first among the Streptomycetes to be completely sequenced (2).Streptomyces bacteria grow by tip extension and hyphal branching to form a dense mycelial network of vegetative hyphae. In response to nutrient depletion and other signals, the vegetative mycelium is partially self-cannibalized by a nuclease(s) and protease(s) to supply nutrients for the growth of aerial hyphae, which subsequently transform into long chains of spores (3,27). This morphological differentiation, which is usually accompanied by the production of secondary metabolite(s), is controlled by multilevel regulatory mechanisms. A key coordinating role in the regulation of morphological differentiation is played by the protein AdpA, which was originally discovered in Streptomyces griseus (37,38). In all Streptomyces genomes sequenced so far, translation of adpA mRNA depends on a leucyl-tRNA for a rarely used TTA codon; the tRNA UAA Leu is encoded by the bldA gene required for aerial mycelium formation. AdpA belongs to the AraC/XylS family of transcription regulators, whose members contain a dual helix-turn-helix (HTH) motif in the C-terminal DNA binding domain. In S. griseus, AdpA activates a number of genes whose products are required for morphological development and for secondary metabolites synthesis (e.g., streptomycin) (12, 28). During vegetative growth, the transcription of S. griseus adpA (adpA Sg ) is repressed by ArpA, the receptor protein for the signal...

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“…This phenotype was reminiscent of the ⌬adpA mutant, which also shows the bald phenotype from many Streptomyces species, including S. coelicolor, S. griseus, etc. (11,12).…”

Altered desferrioxamine-mediated iron utilization is a common trait of bald mutants of Streptomyces coelicolor

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Angucyclines as signals modulate the behaviors of Streptomyces coelicolor

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