scholarly journals Role of Phosphopantetheinyl Transferase Genes in Antibiotic Production by Streptomyces coelicolor

2008 ◽  
Vol 190 (20) ◽  
pp. 6903-6908 ◽  
Author(s):  
Ya-Wen Lu ◽  
Adrianna K. San Roman ◽  
Amy M. Gehring
Keyword(s):  
Antibiotic Production ◽  
Streptomyces Coelicolor ◽  
Morphological Development ◽  
Phosphopantetheinyl Transferase ◽  
Calcium Dependent ◽  
Actinorhodin Production

ABSTRACT The phosphopantetheinyl transferase genes SCO5883 (redU) and SCO6673 were disrupted in Streptomyces coelicolor. The redU mutants did not synthesize undecylprodigiosin, while SCO6673 mutants failed to produce calcium-dependent antibiotic. Neither gene was essential for actinorhodin production or morphological development in S. coelicolor, although their mutation could influence these processes.

Deletion of TerD-domain-encoding genes: effect on Streptomyces coelicolor development

2012 ◽  
Vol 58 (10) ◽  
pp. 1221-1229 ◽  
Author(s):  
Édith Sanssouci ◽  
Sylvain Lerat ◽  
François Daigle ◽  
Gilles Grondin ◽  
François Shareck ◽  
...  
Keyword(s):  
Liquid Medium ◽  
Potential Role ◽  
Solid Medium ◽  
Antibiotic Production ◽  
Streptomyces Coelicolor ◽  
Developmental Patterns ◽  
Small Colony ◽  
Encoding Genes ◽  
Actinorhodin Production

TerD-domain-encoding genes (tdd genes) are highly represented in the Streptomyces coelicolor genome. One of these, the tdd8 gene, was recently shown to have a crucial influence on growth, differentiation, and spore development of this filamentous bacterium. The investigation of the potential role of tdd genes has been extended here to tdd7 (SCO2367) and tdd13 (SCO4277). Both genes are highly expressed in bacteria grown in liquid-rich medium (tryptic soy broth). However, the deletion of these genes in S. coelicolor showed contrasting effects regarding developmental patterns, sporulation, and antibiotic production. Deletion of the tdd7 gene induced a reduction of growth in liquid medium, wrinkling of the mycelium on solid medium, and poor spore and actinorhodin production. On the other hand, deletion of the tdd13 gene did not significantly affect growth in liquid medium but induced a small colony phenotype on solid medium with abundant sporulation and overproduction of undecylprodigiosin. Although their exact functions remain undefined, the present data suggest a major involvement of TerD proteins in the proper development of S. coelicolor.

An aberrant protein synthesis activity is linked with antibiotic overproduction in rpsL mutants of Streptomyces coelicolor A3(2)

Microbiology ◽  
2003 ◽  
Vol 149 (11) ◽  
pp. 3299-3309 ◽  
Author(s):  
Yoshiko Okamoto-Hosoya ◽  
Takeshi Hosaka ◽  
Kozo Ochi
Keyword(s):  
Protein Synthesis ◽  
Antibiotic Production ◽  
Streptomyces Coelicolor ◽  
Translation System ◽  
In The Wild ◽  
Synthesis Activity ◽  
Aberrant Protein ◽  
Ribosomal Protein S12 ◽  
High Level ◽  
Actinorhodin Production

Certain mutations in the rpsL gene (encoding the ribosomal protein S12) activate or enhance antibiotic production in various bacteria. K88E and P91S rpsL mutants of Streptomyces coelicolor A3(2), with an enhanced actinorhodin production, were found to exhibit an aberrant protein synthesis activity. While a high level of this activity (as determined by the incorporation of labelled leucine) was detected at the late stationary phase in the mutants, it decreased with age of the cells in the wild-type strain. In addition, the aberrant protein synthesis was particularly pronounced when cells were subjected to amino acid shift-down, and was independent of their ability to accumulate ppGpp. Ribosomes of K88E and P91S mutants displayed an increased accuracy in protein synthesis as demonstrated by the poly(U)-directed cell-free translation system, but so did K43N, K43T, K43R and K88R mutants, which were streptomycin resistant but showed no effect on actinorhodin production. This eliminates the possibility that the increased accuracy level is a cause of the antibiotic overproduction in the K88E and P91S mutants. The K88E and P91S mutant ribosomes exhibited an increased stability of the 70S complex under low concentrations of magnesium. The authors propose that the aberrant activation of protein synthesis caused by the increased stability of the ribosome is responsible for the remarkable enhancement of antibiotic production in the K88E and P91S mutants.

scholarly journals The global role of ppGpp synthesis in morphological differentiation and antibiotic production in Streptomyces coelicolor A3(2)

2007 ◽  
Vol 8 (8) ◽  
pp. R161 ◽  
Author(s):  
Andrew Hesketh ◽  
Wenqiong Chen ◽  
Jamie Ryding ◽  
Sherman Chang ◽  
Mervyn Bibb
Keyword(s):  
Antibiotic Production ◽  
Streptomyces Coelicolor ◽  
Morphological Differentiation

scholarly journals Transcriptome Analysis of an Antibiotic Downregulator Mutant and Synergistic Actinorhodin Stimulation via Disruption of a Precursor Flux Regulator inStreptomyces coelicolor

2011 ◽  
Vol 77 (5) ◽  
pp. 1872-1877 ◽  
Author(s):  
Seon-Hye Kim ◽  
Han-Na Lee ◽  
Hye-Jin Kim ◽  
Eung-Soo Kim
Keyword(s):  
Microarray Analysis ◽  
Transcriptome Analysis ◽  
Carbon Flux ◽  
Antibiotic Production ◽  
Streptomyces Coelicolor ◽  
Actinorhodin Production

ABSTRACTThrough microarray analysis of an antibiotic-downregulator-deletedStreptomyces coelicolorΔwblAΔSCO1712 mutant, 28wblA- and SCO1712-dependent genes were identified and characterized. Among 14wblA- and SCO1712-independent genes, a carbon flux regulating 6-phosphofructokinase SCO5426 was additionally disrupted in the ΔwblAΔSCO1712 mutant and further stimulated actinorhodin production inS. coelicolor, implying that both regulatory and precursor flux pathways could be synergistically optimized for antibiotic production.

scholarly journals The Heat Shock Repressor HspR Directly Controls Avermectin Production, Morphological Development, and H 2 O 2 Stress Response in Streptomyces avermitilis

2021 ◽  
Author(s):  
Xiaorui Lu ◽  
Qian Wang ◽  
Mengyao Yang ◽  
Zhi Chen ◽  
Jilun Li ◽  
...  
Keyword(s):  
Heat Shock ◽  
Stress Responses ◽  
Cellular Response ◽  
Antibiotic Production ◽  
Streptomyces Avermitilis ◽  
Morphological Development ◽  
Biological Processes ◽  
Transcriptional Repressors ◽  
Important Species

Heat shock response (HSR) is a universal cellular response that promotes survival following temperature increase. In filamentous Streptomyces , which account for ∼70% commercial antibiotic production, HSR is regulated by transcriptional repressors; in particular, the widespread MerR-family regulator HspR has been identified as a key repressor. However, functions of HspR in other biological processes are unknown. The present study demonstrates that HspR pleiotropically controls avermectin production, morphological development, and heat shock and H 2 O 2 stress responses in industrially important species S. avermitilis . HspR directly activated ave structural genes ( aveA1 , aveA2 ) and H 2 O 2 stress-related genes ( katA1 , catR , katA3 , oxyR , ahpC , ahpD ), whereas it directly repressed heat shock genes (HSGs) ( dnaK1-grpE1-dnaJ1-hspR operon, clpB1p , clpB2p , lonAp ) and developmental genes ( wblB , ssgY , ftsH ). HspR interacted with PhoP (response regulator of the widespread PhoPR two-component system) at dnaK1p to co-repress the important dnaK1-grpE1-dnaJ1-hspR operon. PhoP exclusively repressed target HSGs ( htpG , hsp18_1 , hsp18_2 ) different from those of HspR ( clpB1p , clpB2p , lonAp ). A consensus HspR-binding site, 5′-TTGANBBNNHNNNDSTSHN-3′, was identified within HspR target promoter regions, allowing prediction of the HspR regulon involved in broad cellular functions. Taken together, our findings demonstrate a key role of HspR in coordination of a variety of important biological processes in Streptomyces species. IMPORTANCE Our findings are significant to clarify the molecular mechanisms underlying HspR function in Streptomyces antibiotic production, development, and H 2 O 2 stress responses through direct control of its target genes associated with these biological processes. HspR homologs described to date function as transcriptional repressors, but not as activators. Results of the present study demonstrate that HspR acts as a dual repressor/activator. PhoP was shown to crosstalk with HspR at dnaK1p to co-regulate HSR and have its exclusive target HSGs. The novel role of PhoP in HSR further demonstrates the importance of this regulator in Streptomyces . Overexpression of hspR strongly enhanced avermectin production in S. avermitilis wild-type and industrial strains. These findings provide new insights into the regulatory roles and mechanisms of HspR and PhoP, and facilitate methods for antibiotic overproduction in Streptomyces species.

scholarly journals Phosphorylated AbsA2 Negatively Regulates Antibiotic Production in Streptomyces coelicolor through Interactions with Pathway-Specific Regulatory Gene Promoters

2007 ◽  
Vol 189 (14) ◽  
pp. 5284-5292 ◽  
Author(s):  
Nancy L. McKenzie ◽  
Justin R. Nodwell
Keyword(s):  
Response Regulator ◽  
Antibiotic Production ◽  
Streptomyces Coelicolor ◽  
Regulatory Gene ◽  
Gene Clusters ◽  
Negative Regulator ◽  
Gene Promoters ◽  
Promoter Regions ◽  
Calcium Dependent

ABSTRACT The AbsA two-component signal transduction system, comprised of the sensor kinase AbsA1 and the response regulator AbsA2, acts as a negative regulator of antibiotic production in Streptomyces coelicolor, for which the phosphorylated form of AbsA2 (AbsA2∼P) is the agent of repression. In this study, we used chromatin immunoprecipitation to show that AbsA2 binds the promoter regions of actII-ORF4, cdaR, and redZ, which encode pathway-specific activators for actinorhodin, calcium-dependent antibiotic, and undecylprodigiosin, respectively. We confirm that these interactions also occur in vitro and that the binding of AbsA2 to each gene is enhanced by phosphorylation. Induced expression of actII-ORF4 and redZ in the hyperrepressive absA1 mutant (C542) brought about pathway-specific restoration of actinorhodin and undecylprodigiosin production, respectively. Our results suggest that AbsA2∼P interacts with as many as four sites in the region that includes the actII-ORF4 promoter. These data suggest that AbsA2∼P inhibits antibiotic production by directly interfering with the expression of pathway-specific regulators of antibiotic biosynthetic gene clusters.

scholarly journals EshA Accentuates ppGpp Accumulation and Is Conditionally Required for Antibiotic Production in Streptomyces coelicolor A3(2)

2006 ◽  
Vol 188 (13) ◽  
pp. 4952-4961 ◽  
Author(s):  
Natsumi Saito ◽  
Jun Xu ◽  
Takeshi Hosaka ◽  
Susumu Okamoto ◽  
Hiroyuki Aoki ◽  
...  
Keyword(s):  
Type Strain ◽  
Wild Type Strain ◽  
Antibiotic Production ◽  
Streptomyces Coelicolor ◽  
Molecular Signaling ◽  
Wild Type ◽  
Nucleotide Binding Domain ◽  
In The Wild ◽  
Actinorhodin Production ◽  
Cyclic Nucleotide Binding Domain

ABSTRACT Disruption of eshA, which encodes a 52-kDa protein that is produced late during the growth of Streptomyces coelicolor A3(2), resulted in elimination of actinorhodin production. In contrast, disruption of eshB, a close homologue of eshA, had no effect on antibiotic production. The eshA disruptant accumulated lower levels of ppGpp than the wild-type strain accumulated. The loss of actinorhodin production in the eshA disruptant was restored by expression of a truncated relA gene, which increased the ppGpp level to the level in the wild-type strain, indicating that the reduced ppGpp accumulation in the eshA mutant was solely responsible for the loss of antibiotic production. Antibiotic production was also restored in the eshA mutant by introducing mutations into rpoB (encoding the RNA polymerase β subunit) that bypassed the requirement for ppGpp, which is consistent with a role for EshA in modulating ppGpp levels. EshA contains a cyclic nucleotide-binding domain that is essential for its role in triggering actinorhodin production. EshA may provide new insights and opportunities to unravel the molecular signaling events that occur during physiological differentiation in streptomycetes.

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