Streptomyces
Over the last century, Streptomyces bacteria – and their metabolic products – have revolutionized modern medicine. These little pharmaceutical factories produce a vast array of natural products that have been co-opted for medical and agricultural therapies. In addition to their metabolic sophistication, Streptomyces also exhibit remarkable developmental and regulatory complexity.
Guest-edited by Dr Marie Elliot, this collection of keynote research articles will highlight fascinating aspects of Streptomyces biology, and the advances that are providing us with newfound insight and appreciation for these extraordinary bacteria.
Collection Contents
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Gene ssfg_01967 (miaB) for tRNA modification influences morphogenesis and moenomycin biosynthesis in Streptomyces ghanaensis ATCC14672
Streptomyces ghanaensis ATCC14672 is remarkable for its production of phosphoglycolipid compounds, moenomycins, which serve as a blueprint for the development of a novel class of antibiotics based on inhibition of peptidoglycan glycosyltransferases. Here we employed mariner transposon (Tn) mutagenesis to find new regulatory genes essential for moenomycin production. We generated a library of 3000 mutants which were screened for altered antibiotic activity. Our focus centred on a single mutant, HIM5, which accumulated lower amounts of moenomycin and was impaired in morphogenesis as compared to the parental strain. HIM5 carried the Tn insertion within gene ssfg_01967 for putative tRNA (N6-isopentenyl adenosine(37)-C2)-methylthiotransferase, or MiaB, and led to a reduced level of thiomethylation at position 37 in the anticodon of S. ghanaensis transfer ribonucleic acid (tRNA). It is likely that the mutant phenotype of HIM5 stems from the way in which ssfg_01967::Tn influences translation of the rare leucine codon UUA in several genes for moenomycin production and life cycle progression in S. ghanaensis . This is the first report showing that quantitative changes in tRNA modification status in Streptomyces have physiological consequences.
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GlnR and PhoP regulate β-glucosidases involved in cellulose digestion in response to nitrogen and phosphate availability
Ya Xu and Bang-Ce YeThe limited catalytic efficiency of cellulose-degrading enzymes restricts cellulose digestion. We investigated the transcriptional regulation of genes encoding key cellulose degrading enzymes, namely β-glucosidases, in the industrial actinobacterium Saccharopolyspora erythraea. We observed that the expression of most β-glucosidase-encoding genes was controlled by the availability of nitrogen and phosphate via their respective global regulators, namely GlnR and PhoP. Electrophoretic mobility shift assay demonstrated that GlnR and PhoP bound directly to the promoters of β-glucosidase-encoding genes. Deletion of glnR resulted in lower transcript levels and activity of β-glucosidases, leading to decreased bacterial growth on cellulose. Overexpression of glnR and phoP or nitrogen/phosphate starvation increased the transcript levels and total activity of β-glucosidases. Moreover, GlnR/PhoP-mediated cellobiose utilization was also observed in Streptomyces coelicolor A3(2). These findings provide insights into the regulatory roles played by GlnR and PhoP in coordinating nitrogen/phosphate metabolism and carbohydrate utilization, and indicate potential strategies for cellulose fermentation in the production of bio-based chemicals by actinobacteria.
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GntR family regulator SCO6256 is involved in antibiotic production and conditionally regulates the transcription of myo-inositol catabolic genes in Streptomyces coelicolor A3(2)
More LessSCO6256 belongs to the GntR family and shows 74 % identity with SCO6974, which is the repressor of myo-inositol catabolism in Streptomyces coelicolor A3(2). Disruption of SCO6256 significantly enhanced the transcription of myo-inositol catabolic genes in R2YE medium. The purified recombinant SCO6256 directly bound to the upstream regions of SCO2727, SCO6978 and SCO6985, as well as its encoding gene. Footprinting assays demonstrated that SCO6256 bound to the same sites in the myo-inositol catabolic gene cluster as SCO6974. The expression of SCO6256 was repressed by SCO6974 in minimal medium with myo-inositol as the carbon source, but not in R2YE medium. Glutathione-S-transferase pull-down assays demonstrated that SCO6974 and SCO6256 interacted with each other; and both of the proteins controlled the transcription of myo-inositol catabolic genes in R2YE medium. These results indicated SCO6256 regulates the transcription of myo-inositol catabolic genes in coordination with SCO6974 in R2YE medium. In addition, SCO6256 negatively regulated the production of actinorhodin and calcium-dependent antibiotic via control of the transcription of actII-ORF4 and cdaR. SCO6256 bound to the upstream region of cdaR and the binding sequence was proved to be TTTCGGCACGCAGACAT, which was further confirmed through base substitution. Four putative targets (SCO2652, SCO4034, SCO4237 and SCO6377) of SCO6256 were found by screening the genome sequence of Strep. coelicolor A3(2) based on the conserved binding motif, and confirmed by transcriptional analysis and electrophoretic mobility shift assays. These results revealed that SCO6256 is involved in the regulation of myo-inositol catabolic gene transcription and antibiotic production in Strep. coelicolor A3(2).
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Genetic Studies of the Fertility Plasmid SCP2 and its SCP2* Variants in Streptomyces coelicolor A3(2)
More LessThe plasmid SCP2, initially discovered through the occurrence of a high fertility variant, SCP2*, is a self-transmissible fertility factor capable of promoting chromosomal recombination within Streptomyces coelicolor A3(2). Further high fertility variants of SCP2, similar to SCP2*, were isolated from amongst the recombinants produced in matings involving SCP2, and their genetic properties were compared. SCP2 and its derivatives elicit lethal zygosis on transfer into an SCP2− recipient; this plasmid-determined phenotype allowed the isolation of SCP2− strains and the detection of the interspecific transfer of SCP2* by mating from S. coelicolor to Streptomyces parvulus and Streptomyces lividans, whereupon it underwent stable maintenance. The transfer genes of SCP2 and SCP2*, which are not normally fully expressed, were shown to undergo transient derepression on entry into an SCP2− strain. An ‘entry disadvantage’ system determined by SCP2 and SCP2* was recognized.
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