ArticleJournal of bacteriology2013
SsaA, a member of a novel class of transcriptional regulators, controls sansanmycin production in Streptomyces sp. strain SS through a feedback mechanism.
Article in Journal of bacteriology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Coelimycin inside out - negative feedback regulation by its intracellular precursors.Applied microbiology and biotechnology · 2024Article
- New insights into the dihydro-mureidomycin biosynthesis controlled by two unusual proteins in Streptomyces roseosporus.Microbial cell factories · 2023Article
- Biosynthesis of the fungal nonribosomal peptide penilumamide A and biochemical characterization of a pterin-specific adenylation domain.RSC chemical biology · 2023Article
- Molecular mechanism of mureidomycin biosynthesis activated by introduction of an exogenous regulatory gene ssaA into Streptomyces roseosporus.Science China. Life sciences · 2021Article
- Identification and characterization of enzymes involved in the biosynthesis of pyrimidine nucleoside antibiotics.Natural product reports · 2021Review
- Blocks in the pseudouridimycin pathway unlock hidden metabolites in the Streptomyces producer strain.Scientific reports · 2021Article
- Coordinated regulation for nature products discovery and overproduction inSynthetic and systems biotechnology · 2020Article
- The regulatory cascades of antibiotic production in Streptomyces.World journal of microbiology & biotechnology · 2020Review
- The Application of Regulatory Cascades inFrontiers in microbiology · 2020Review
- Corrigendum: The Application of Regulatory Cascades inFrontiers in microbiology · 2020Article
- Rescrutiny of the sansanmycin biosynthetic gene cluster leads to the discovery of a novel sansanmycin analogue with more potency against Mycobacterium tuberculosis.The Journal of antibiotics · 2019Article
- LmbU, a Cluster-Situated Regulator for Lincomycin, Consists of a DNA-Binding Domain, an Auto-Inhibitory Domain, and Forms Homodimer.Frontiers in microbiology · 2019Article
- Chemical Elicitors of Antibiotic Biosynthesis in Actinomycetes.Microorganisms · 2018Review
- Regulatory genes and their roles for improvement of antibiotic biosynthesis in Streptomyces.3 Biotech · 2017Review
- Nature's combinatorial biosynthesis and recently engineered production of nucleoside antibiotics in Streptomyces.World journal of microbiology & biotechnology · 2017Review
- Improving the N-terminal diversity of sansanmycin through mutasynthesis.Microbial cell factories · 2016Article
- Natural and engineered biosynthesis of nucleoside antibiotics in Actinomycetes.Journal of industrial microbiology & biotechnology · 2016Review
- Identification of novel mureidomycin analogues via rational activation of a cryptic gene cluster in Streptomyces roseosporus NRRL 15998.Scientific reports · 2015Article
- Functional manipulations of the tetramycin positive regulatory gene ttmRIV to enhance the production of tetramycin A and nystatin A1 in Streptomyces ahygroscopicus.Journal of industrial microbiology & biotechnology · 2015Article
- Two Master Switch Regulators Trigger A40926 Biosynthesis in Nonomuraea sp. Strain ATCC 39727.Journal of bacteriology · 2015Article
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6 authors.
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Abstract
Sansanmycins, produced by Streptomyces sp. strain SS, are uridyl peptide antibiotics with activities against Pseudomonas aeruginosa and multidrug-resistant Mycobacterium tuberculosis. In this work, the biosynthetic gene cluster of sansanmycins, comprised of 25 open reading frames (ORFs) showing considerable amino acid sequence identity to those of the pacidamycin and napsamycin gene cluster, was identified. SsaA, the archetype of a novel class of transcriptional regulators, was characterized in the sansanmycin gene cluster, with an N-terminal fork head-associated (FHA) domain and a C-terminal LuxR-type helix-turn-helix (HTH) motif. The disruption of ssaA abolished sansanmycin production, as well as the expression of the structural genes for sansanmycin biosynthesis, indicating that SsaA is a pivotal activator for sansanmycin biosynthesis. SsaA was proved to directly bind several putative promoter regions of biosynthetic genes, and comparison of sequences of the binding sites allowed the identification of a consensus SsaA binding sequence, GTMCTGACAN₂TGTCAGKAC. The DNA binding activity of SsaA was inhibited by sansanmycins A and H in a concentration-dependent manner. Furthermore, sansanmycins A and H were found to directly interact with SsaA. These results indicated that SsaA strictly controls the production of sansanmycins at the transcriptional level in a feedback regulatory mechanism by sensing the accumulation of the end products. As the first characterized regulator of uridyl peptide antibiotic biosynthesis, the understanding of this autoregulatory process involved in sansanmycin biosynthesis will likely provide an effective strategy for rational improvements in the yields of these uridyl peptide antibiotics.
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