Design of mineral medium for growth of Actinomadura sp. ATCC 39727, producer of the glycopeptide A40926: effects of calcium ions and nitrogen sources

Technikova-Dobrova, Zuzana; Damiano, Fabrizio; Tredici, Salvatore Maurizio; Vigliottá, Giovanni; Summa, Roberta di; Palese, Luigi Leonardo; Abbrescia, Anna; Labonia, N.; Gnoni, Gabriele V.; Alifano, Pietro

doi:10.1007/s00253-004-1626-2

Cited by 32 publications

(27 citation statements)

References 9 publications

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“…Up-regulation of cluster 15 may be part of this strategy because tabtoxin-like β-lactams inhibit the glutamine synthetase of organisms competing for ammonium. The strict interplay between nitrogen and secondary metabolism is in agreement with previous data 7, 41, 42 .…”

Section: Discussionsupporting

confidence: 92%

The complete 12 Mb genome and transcriptome of Nonomuraea gerenzanensis with new insights into its duplicated “magic” RNA polymerase

D’Argenio

Petrillo

Pasanisi

et al. 2016

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In contrast to the widely accepted consensus of the existence of a single RNA polymerase in bacteria, several actinomycetes have been recently shown to possess two forms of RNA polymerases due the to co-existence of two rpoB paralogs in their genome. However, the biological significance of the rpoB duplication is obscure. In this study we have determined the genome sequence of the lipoglycopeptide antibiotic A40926 producer Nonomuraea gerenzanensis ATCC 39727, an actinomycete with a large genome and two rpoB genes, i.e. rpoB(S) (the wild-type gene) and rpoB(R) (the mutant-type gene). We next analyzed the transcriptional and metabolite profiles in the wild-type gene and in two derivative strains over-expressing either rpoB(R) or a mutated form of this gene to explore the physiological role and biotechnological potential of the “mutant-type” RNA polymerase. We show that rpoB(R) controls antibiotic production and a wide range of metabolic adaptive behaviors in response to environmental pH. This may give interesting perspectives also with regard to biotechnological applications.

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Section: Discussionsupporting

confidence: 92%

The complete 12 Mb genome and transcriptome of Nonomuraea gerenzanensis with new insights into its duplicated “magic” RNA polymerase

D’Argenio

Petrillo

Pasanisi

et al. 2016

Sci Rep

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“…In particular, Gunnarsson et al (12) found that low initial phosphate concentrations were beneficial for A40926 production and that the onset of production was not governed by the residual phosphate concentration, although its level strongly influenced production rates and final titers. These results were independently confirmed by Technikova-Dobrova et al (42). The molecular bases for phosphate regulation of A40926 production have not yet been studied.…”

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confidence: 63%

“…Other StrR-like regulators have been characterized, such as NovG from the Streptomyces caeruleus novobiocin cluster (10), CloG from the Streptomyces roseochromogenes clorobiocin cluster (10), and KasT from the Streptomyces kasugaensis kasugamycin cluster (13). Recently, the production of A40926 was found to be influenced by phosphate (12,42). In particular, Gunnarsson et al (12) found that low initial phosphate concentrations were beneficial for A40926 production and that the onset of production was not governed by the residual phosphate concentration, although its level strongly influenced production rates and final titers.…”

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confidence: 99%

Phosphate-Controlled Regulator for the Biosynthesis of the Dalbavancin Precursor A40926

et al. 2007

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The actinomycete Nonomuraea sp. strain ATCC 39727 produces the glycopeptide A40926, the precursor of the novel antibiotic dalbavancin. Previous studies have shown that phosphate limitation results in enhanced A40926 production. The A40926 biosynthetic gene (dbv) cluster, which consists of 37 genes, encodes two putative regulators, Dbv3 and Dbv4, as well as the response regulator (Dbv6) and the sensor-kinase (Dbv22) of a putative two-component system. Reverse transcription-PCR (RT-PCR) and real-time RT-PCR analysis revealed that the dbv14-dbv8 and the dbv30-dbv35 operons, as well as dbv4, were negatively influenced by phosphate. Dbv4 shows a putative helix-turn-helix DNA-binding motif and shares sequence similarity with StrR, the transcriptional activator of streptomycin biosynthesis in Streptomyces griseus. Dbv4 was expressed in Escherichia coli as an N-terminal His 6 -tagged protein. The purified protein bound the dbv14 and dbv30 upstream regions but not the region preceding dbv4. Bbr, a Dbv4 ortholog from the gene cluster for the synthesis of the glycopeptide balhimycin, also bound to the dbv14 and dbv30 upstream regions, while Dbv4 bound appropriate regions from the balhimycin cluster. Our results provide new insights into the regulation of glycopeptide antibiotics, indicating that the phosphate-controlled regulator Dbv4 governs two key steps in A40926 biosynthesis: the biosynthesis of the nonproteinogenic amino acid 3,5-dihydroxyphenylglycine and critical tailoring reactions on the heptapeptide backbone.

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“…Yeast-starch medium was used for growth, and culture conditions were as reported previously (36). S. lividans strains 1326 (wild type), KO-421 (relC), and KO-422 (relC rif1) used in this study were described previously (18,20).…”

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Activation of Dormant Bacterial Genes byNonomuraeasp. Strain ATCC 39727 Mutant-Type RNA Polymerase

et al. 2009

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There is accumulating evidence that the ability of actinomycetes to produce antibiotics and other bioactive secondary metabolites has been underestimated due to the presence of cryptic gene clusters. The activation of dormant genes is therefore one of the most important areas of experimental research for the discovery of drugs in these organisms. The recent observation that several actinomycetes possess two RNA polymerase ␤-chain genes (rpoB) has opened up the possibility, explored in this study, of developing a new strategy to activate dormant gene expression in bacteria. Two rpoB paralogs, rpoB(S) and rpoB(R), provide Nonomuraea sp. strain ATCC 39727 with two functionally distinct and developmentally regulated RNA polymerases. The product of rpoB(R), the expression of which increases after transition to stationary phase, is characterized by five amino acid substitutions located within or close to the so-called rifampin resistance clusters that play a key role in fundamental activities of RNA polymerase. Here, we report that rpoB(R) markedly activated antibiotic biosynthesis in the wild-type Streptomyces lividans strain 1326 and also in strain KO-421, a relaxed (rel) mutant unable to produce ppGpp. Site-directed mutagenesis demonstrated that the rpoB(R)-specific missense H426N mutation was essential for the activation of secondary metabolism. Our observations also indicated that mutant-type or duplicated, rpoB often exists in nature among rare actinomycetes and will thus provide a basis for further basic and applied research.

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Design of mineral medium for growth of Actinomadura sp. ATCC 39727, producer of the glycopeptide A40926: effects of calcium ions and nitrogen sources

Cited by 32 publications

References 9 publications

The complete 12 Mb genome and transcriptome of Nonomuraea gerenzanensis with new insights into its duplicated “magic” RNA polymerase

The complete 12 Mb genome and transcriptome of Nonomuraea gerenzanensis with new insights into its duplicated “magic” RNA polymerase

Phosphate-Controlled Regulator for the Biosynthesis of the Dalbavancin Precursor A40926

Activation of Dormant Bacterial Genes byNonomuraeasp. Strain ATCC 39727 Mutant-Type RNA Polymerase

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