Dataset Information

Transcriptome analysis of an antibiotic downregulator mutant and synergistic Actinorhodin stimulation via disruption of a precursor flux regulator in Streptomyces coelicolor.

ABSTRACT: Through microarray analysis of an antibiotic-downregulator-deleted Streptomyces coelicolor ?wblA ?SCO1712 mutant, 28 wblA- and SCO1712-dependent genes were identified and characterized. Among 14 wblA- and SCO1712-independent genes, a carbon flux regulating 6-phosphofructokinase SCO5426 was additionally disrupted in the ?wblA ?SCO1712 mutant and further stimulated actinorhodin production in S. coelicolor, implying that both regulatory and precursor flux pathways could be synergistically optimized for antibiotic production.

SUBMITTER: Kim SH

PROVIDER: S-EPMC3067302 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Transcriptome analysis of an antibiotic downregulator mutant and synergistic Actinorhodin stimulation via disruption of a precursor flux regulator in Streptomyces coelicolor.

Kim Seon-Hye SH Lee Han-Na HN Kim Hye-Jin HJ Kim Eung-Soo ES

Applied and environmental microbiology 20110107 5

Through microarray analysis of an antibiotic-downregulator-deleted Streptomyces coelicolor ΔwblA ΔSCO1712 mutant, 28 wblA- and SCO1712-dependent genes were identified and characterized. Among 14 wblA- and SCO1712-independent genes, a carbon flux regulating 6-phosphofructokinase SCO5426 was additionally disrupted in the ΔwblA ΔSCO1712 mutant and further stimulated actinorhodin production in S. coelicolor, implying that both regulatory and precursor flux pathways could be synergistically optimized ...[more]

PMID: 21216912

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Project description:The transcription factor AdpA is a key regulator controlling both secondary metabolism and morphological differentiation in Streptomyces. Due to its critical functions, its expression undergoes multilevel regulations at transcriptional, posttranscriptional, and translational levels, yet no posttranslational regulation has been reported. Sulfane sulfur, such as hydro polysulfide (HSnH, n ≥ 2) and organic polysulfide (RSnH, n ≥ 2), is common inside microorganisms, but its physiological functions are largely unclear. Here, we discovered that sulfane sulfur posttranslationally modifies AdpA in Streptomyces coelicolor via specifically reacting with Cys62 of AdpA to form a persulfide (Cys62-SSH). This modification decreases the affinity of AdpA to its self-promoter PadpA, allowing increased expression of adpA, further promoting the expression of its target genes actII-4 and wblA. ActII-4 activates actinorhodin biosynthesis, and WblA regulates morphological development. Bioinformatics analyses indicated that AdpA-Cys62 is highly conserved in Streptomyces, suggesting the prevalence of such modification in this genus. Thus, our study unveils a new type of regulation on the AdpA activity and sheds a light on how sulfane sulfur stimulates the production of antibiotics in Streptomyces. IMPORTANCE Streptomyces species produce a myriad of natural products with (potential) clinical applications. While the database of biosynthetic gene clusters is quickly expanding, their regulation mechanisms are rarely known. Sulfane sulfur species are commonly present in microorganisms with unclear functions. Here, we discovered that sulfane sulfur increases actinorhodin (ACT) production in S. coelicolor. The underlying mechanism is that sulfane sulfur specifically reacts with AdpA, a global transcription factor controlling both ACT gene cluster and morphological differentiation-related genes, to form sulfhydrated AdpA. This modification changes the dynamics of AdpA-controlled gene networks and leads to high expression of ACT biosynthetic genes. Given the wide prevalence of AdpA and sulfane sulfur in Streptomyces, this mechanism may represent a common regulating pattern of all AdpA-controlled biosynthetic pathways. Thus, this finding provides a new strategy for mining and activating valuable biosynthetic gene clusters.

Dataset Information

Transcriptome analysis of an antibiotic downregulator mutant and synergistic Actinorhodin stimulation via disruption of a precursor flux regulator in Streptomyces coelicolor.

Publications

Transcriptome analysis of an antibiotic downregulator mutant and synergistic Actinorhodin stimulation via disruption of a precursor flux regulator in Streptomyces coelicolor.

Similar Datasets

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