Autoregulation of hpdR and its effect on CDA biosynthesis in Streptomyces coelicolor

Yang, Haihua; An, Yang; Wang, Linqi; Zhang, Shuli; Zhang, Yue; Tian, Yun; Liu, Gang; Tan, Huarong

doi:10.1099/mic.0.038604-0

Cited by 7 publications

(5 citation statements)

References 24 publications

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“…Repression is relieved by 4HPP (111). Remarkably, HpdR also binds to the promoter of the CDA biosynthetic gene hmaS, which encodes an enzyme converting 4HPP to 4-hydroxymandelate (112). Since hmaS transcription is reduced in an hpdR mutant, HpdR functions to activate hmaS.…”

Section: Regulation At a Meeting Point Of Primary And Secondary Metabmentioning

confidence: 99%

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Molecular Regulation of Antibiotic Biosynthesis in Streptomyces

Liu

Chater

Chandra

et al. 2013

Microbiol Mol Biol Rev

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592

536

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SUMMARY Streptomycetes are the most abundant source of antibiotics. Typically, each species produces several antibiotics, with the profile being species specific. Streptomyces coelicolor , the model species, produces at least five different antibiotics. We review the regulation of antibiotic biosynthesis in S. coelicolor and other, nonmodel streptomycetes in the light of recent studies. The biosynthesis of each antibiotic is specified by a large gene cluster, usually including regulatory genes (cluster-situated regulators [CSRs]). These are the main point of connection with a plethora of generally conserved regulatory systems that monitor the organism's physiology, developmental state, population density, and environment to determine the onset and level of production of each antibiotic. Some CSRs may also be sensitive to the levels of different kinds of ligands, including products of the pathway itself, products of other antibiotic pathways in the same organism, and specialized regulatory small molecules such as gamma-butyrolactones. These interactions can result in self-reinforcing feed-forward circuitry and complex cross talk between pathways. The physiological signals and regulatory mechanisms may be of practical importance for the activation of the many cryptic secondary metabolic gene cluster pathways revealed by recent sequencing of numerous Streptomyces genomes.

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Section: Regulation At a Meeting Point Of Primary And Secondary Metabmentioning

confidence: 99%

“…Thus, 4HPP acts both as a metabolic intermediate and as a regulatory ligand in the partitioning of tyrosine catabolism between primary and secondary metabolism ( Fig. 7) (112).…”

Section: Regulation At a Meeting Point Of Primary And Secondary Metabmentioning

confidence: 99%

Molecular Regulation of Antibiotic Biosynthesis in Streptomyces

Liu

Chater

Chandra

et al. 2013

Microbiol Mol Biol Rev

Self Cite

592

536

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“…Additional qRT-PCR results revealed that transcription of clmR1 also increases in the clmR1 mutant, suggesting that clmR1 expression is downregulated by its own product. Several examples of negative autoregulation have been described to date, such as the case of heat-shock protein regulator HspR, which negatively regulates its own expression along with that of some other genes coding for different chaperone systems (Salerno et al , 2007), or the IclR-family regulator HpdR, which is involved in calcium-dependent antibiotic production by Streptomyces coelicolor (Yang et al , 2010).…”

Section: Discussionmentioning

confidence: 99%

Collismycin A biosynthesis in Streptomyces sp. CS40 is regulated by iron levels through two pathway-specific regulators

et al. 2014

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Two putative pathway-specific regulators have been identified in the collismycin A gene cluster: ClmR1, belonging to the TetR-family, and the LuxR-family transcriptional regulator ClmR2. Inactivation of clmR1 led to a moderate increase of collismycin A yields along with an early onset of its production, suggesting an inhibitory role for the product of this gene. Inactivation of clmR2 abolished collismycin A biosynthesis, whereas overexpression of ClmR2 led to a fourfold increase in production yields, indicating that ClmR2 is an activator of collismycin A biosynthesis. Expression analyses of the collismycin gene cluster in the wild-type strain and in DclmR1 and DclmR2 mutants confirmed the role proposed for both regulatory genes, revealing that ClmR2 positively controls the expression of most of the genes in the cluster and ClmR1 negatively regulates both its own expression and that of clmR2. Additionally, production assays and further transcription analyses confirmed the existence of a higher regulatory level modulating collismycin A biosynthesis in response to iron concentrations in the culture medium. Thus, high iron levels inhibit collismycin A biosynthesis through the repression of clmR2 transcription. These results have allowed us to propose a regulatory model that integrates the effect of iron as the main environmental stimulus controlling collismycin A biosynthesis.

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“…The calcium-dependent antibiotic (CDA) assay essentially followed that described by Yang et al (24). Inocula of 10 9 spores of M145, JSE2301, JSE2301/pJSE2255, and JSE2301/pIJ8600 were plated on Oxoid nutrient agar (10 ml) and incubated at 30°C for 3 days.…”

Section: Methodsmentioning

confidence: 99%

SCO5745, a Bifunctional RNase J Ortholog, Affects Antibiotic Production in Streptomyces coelicolor

2014

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The bacterial RNases J are considered bifunctional RNases possessing both endo-and exonucleolytic activities. We have isolated an RNase J ortholog from Streptomyces coelicolor encoded by the gene sco5745. We overexpressed a decahistidine-tagged version of SCO5745 and purified the overexpressed protein by immobilized metal ion affinity chromatography. We demonstrated the presence of both 5=-to-3= exonucleolytic and endonucleolytic activities on the Bacillus subtilis thrS transcript. Exonucleoytic activity predominated with 5= monophosphorylated thrS, while endonucleolytic activity predominated with 5= triphosphorylated thrS. While sco5745 is the only RNase J allele in S. coelicolor, the gene is not essential. Its disruption resulted in delayed production of the antibiotic actinorhodin, overproduction of undecylprodigiosin, and diminished production of the calcium-dependent antibiotic, in comparison with the parental strain.T he decay of mRNA and the concomitant regulation of gene expression at this level are controlled by a number of key RNases present in a variety of combinations in both Gram-negative and Gram-positive bacteria. There is growing appreciation of how evolutionarily distant bacteria functionally combine quite different sets of proteins in the regulation of RNA metabolism (1, 2). RNase J was the first of two bacterial RNases discovered to possess both exo-and endonucleolytic activities. RNase BN acts as a 3=-to-5= distributive exonuclease releasing mononucleotides and producing a ladder of digestion products. Cleaving endonucleolytically, it produces short 3=-end fragments. While active on single-stranded substrates, RNase BN prefers duplexed substrates and is inhibited by the presence of a 3=-end phosphoryl group and 3=-CCA sequence (3).Originally characterized by two alleles in Bacillus subtilis (4), RNase J is widely distributed in other Gram-positive species as a single allele, as in Mycobacterium smegmatis (5), and as two alleles in Streptococcus pyogenes (6). RNases J have also been characterized in the Gram-negative bacterium Sinorhizobium (7), in the hyperthermophilic archaea Pyrococcus abyssi and Thermococcus kodakaraensis (8), and in plant chloroplasts (9). B. subtilis expresses two paralogous proteins, RNase J1 and J2. The two proteins possess endo-and exonuclease activities in vitro but are not equally active. Recently, it has been argued that the major function of RNase J1 is as an exonuclease, and no specific function has been assigned to RNase J2. However, the two proteins form a heterotetramer in vivo that cleaves a model substrate at a different site than the J1 homodimer (10). The single-stranded exonuclease activity of RNases J appears to be strongly dependent upon the phosphorylation state of the 5= end of transcripts, usually showing a distinct preference for the monophosphorylated state (4, 9, 11, 12).Streptomycetes are Gram-positive actinomycetes noted for their production of antibiotics, antifungals, and chemotherapeutic drugs (13). Streptomyces coelicolor is a model for the ...

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Autoregulation of hpdR and its effect on CDA biosynthesis in Streptomyces coelicolor

Cited by 7 publications

References 24 publications

Molecular Regulation of Antibiotic Biosynthesis in Streptomyces

Molecular Regulation of Antibiotic Biosynthesis in Streptomyces

Collismycin A biosynthesis in Streptomyces sp. CS40 is regulated by iron levels through two pathway-specific regulators

SCO5745, a Bifunctional RNase J Ortholog, Affects Antibiotic Production in Streptomyces coelicolor

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