Cyclic AMP regulation of tylosin biosynthesis and secondary metabolism in <i>Streptomyces fradiae</i>

Tata, Murthy; Menawat, Anil S.

doi:10.1002/bit.260440305

Cited by 13 publications

(6 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In conclusion, our data, together with those of Susstrunk et al (1998) and Tata & Menawat (1994), show a pleiotropic regulatory role for cAMP in Streptomyces.…”

Section: ~~~ ~-supporting

confidence: 86%

See 1 more Smart Citation

Possible involvement of cAMP in aerial mycelium formation and secondary metabolism in Streptomyces griseus

Kang

Ochi

et al. 1999

Microbiology

View full text Add to dashboard Cite

“…In conclusion, our data, together with those of Susstrunk et al (1998) and Tata & Menawat (1994), show a pleiotropic regulatory role for cAMP in Streptomyces.…”

Section: ~~~ ~-supporting

confidence: 86%

“…The regulatory roles of cyaA in S. coelicolor A3(2) reported recently by Susstrunk et al (1998) suggest that CAMP does act as a second messenger in Streptornyces spp. Tata & Menawat (1994) also reported a role for CAMP in tylosin synthesis in Streptomyces fradiae.…”

Section: ~~~ ~-mentioning

confidence: 94%

Possible involvement of cAMP in aerial mycelium formation and secondary metabolism in Streptomyces griseus

Kang

Ochi

et al. 1999

Microbiology

View full text Add to dashboard Cite

“…141 In addition, dibutiryl cAMP supplementation to cultures of S. fradiae, under conditions of growth limitation by ferric ammonium citrate, stimulates tylosin production by 25-30%. 142 In the same line, variants of this microorganism with high tylosin production contain 20-50% more cAMP than the parental strain. 24 Spore germination, aerial mycelium formation and actinorhodin production are also dependent on cAMP in S. coelicolor.…”

Section: Streptomycesmentioning

confidence: 99%

Carbon source regulation of antibiotic production

et al. 2010

View full text Add to dashboard Cite

“…In the first set of experiments, we tested the DNR precursors acetyl-coenzyme A (CoA) and malonyl-CoA (Fig. 1), two signal transducing molecules (A-factor [31] and cyclic-AMP [45]), and DNR. Among these molecules, only DNR had an effect (Fig.…”

Section: Vol 178 1996mentioning

confidence: 99%

The DnrN protein of Streptomyces peucetius, a pseudo-response regulator, is a DNA-binding protein involved in the regulation of daunorubicin biosynthesis

Furuya

Hutchinson

1996

J Bacteriol

View full text Add to dashboard Cite

Actinomycetes are gram-positive bacteria that possess an interesting life cycle involving morphological differentiation (aerial mycelia and spore formation) and specialized secondary metabolism (antibiotic production). To regulate these complex processes, the bacteria appear to have evolved an intricate regulatory hierarchy with several different mechanisms. Some of these processes are unique to the Streptomyces spp., such as the bldA gene (20), and others are well-known in eukaryotes, such as hormone-like molecules (31) and serine-threonine or tyrosine kinases (24). Other mechanisms resemble ones common in prokaryotes. An increasingly important example of the latter is the two-component system (4, 17, 46, 50), which consists of a histidine kinase that undergoes autophosphorylation in response to environmental or developmental changes and then transfers its phosphate group to an aspartyl residue of a response regulator protein (34,35,40).In our study of the biosynthesis of daunorubicin (DNR) and doxorubicin (DXR), commercially important antitumor drugs (Fig. 1), sequence analysis of the dnrN gene (see Fig. 2) showed that its product is very similar to response regulator proteins of the FixJ subfamily (13,32). The N-terminal region of DnrN has a putative phosphorylation site (D-55) and other conserved sites required for activation by phosphorylation and characteristic of response regulators. However, the D-553E (D55E) and D-553N (D55N) substitutions at the putative site of phosphorylation resulted in a reduction rather than a complete loss of DnrN activity (32). Furthermore, analysis of the 60-kb region sequenced around dnrN has not uncovered a putative sensor kinase gene, which often resides near the response regulator gene. Since DnrN lacks two key characteristics of canonical response regulators, we call it a pseudo-response regulator.Our previous results from mutant complementation (32) and transcriptional analysis (23) experiments showed that dnrN is essential for transcription of the dnrI regulatory gene and functions epistatically with respect to dnrI. DnrI, whose sequence is similar to other Streptomyces regulatory proteins such as AfsR (16), RedD (30), and actII-Orf4 (9), in turn activates the DNR and DXR structural and resistance genes (23). Among streptomycetes, this is a clear case in which a putative response regulator gene is known to govern expression of antibiotic biosynthesis and resistance genes in such a direct and essential manner.In spite of considerable information about response regulator proteins in other bacteria (1,11,37,48), so far none of them have been characterized from streptomycetes. Here we report that the DnrN protein binds specifically to the dnrI promoter region and is not likely to require phosphorylation for its binding. We also show that DNR has a positive effect on the DnrN level in Streptomyces peucetius and suggest how DNR could feedback repress dnrI expression.

show abstract

Cyclic AMP regulation of tylosin biosynthesis and secondary metabolism in Streptomyces fradiae

Cited by 13 publications

References 26 publications

Possible involvement of cAMP in aerial mycelium formation and secondary metabolism in Streptomyces griseus

Possible involvement of cAMP in aerial mycelium formation and secondary metabolism in Streptomyces griseus

Carbon source regulation of antibiotic production

The DnrN protein of Streptomyces peucetius, a pseudo-response regulator, is a DNA-binding protein involved in the regulation of daunorubicin biosynthesis

Contact Info

Product

Resources

About