Stabilization of nucleic acids by unusual polyamines produced by an extreme thermophile, <i>Thermus thermophilus</i>

Terui, Yusuke; Ohnuma, Mio; Hiraga, Kaori; Kawashima, Etsuko; Oshima, Tairo

doi:10.1042/bj20041778

Cited by 118 publications

(88 citation statements)

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“…9C). These long and branched polyamines have a marked effect of protecting and stabilizing nucleic acids (5,6) and of activating cell-free polypeptide synthesis at high temperature (7)(8)(9).…”

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N1-Aminopropylagmatine, a New Polyamine Produced as a Key Intermediate in Polyamine Biosynthesis of an Extreme Thermophile, Thermus thermophilus

Ohnuma

Terui

Tamakoshi

et al. 2005

Journal of Biological Chemistry

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In the extreme thermophile Thermus thermophilus, a disruption mutant of a gene homologous to speB (coding for agmatinase ‫؍‬ agmatine ureohydrolase) accumulated N 1 -aminopropylagmatine (N 8 -amidino-1,8-diamino-4-azaoctane, N 8 -amidinospermidine), a new compound, whereas all other polyamines produced by the wild-type strain were absent from the cells. Double disruption of speB and speE (polyamine aminopropyltransferase) resulted in the disappearance of N 1 -aminopropylagmatine and the accumulation of agmatine. These results suggested the following. 1) N 1 -Aminopropylagmatine is produced from agmatine by the action of an enzyme coded by speE. 2) N 1 -Aminopropylagmatine is a metabolic intermediate in the biosynthesis of unique polyamines found in the thermophile. 3) N 1 -Aminopropylagmatine is a substrate of the SpeB homolog. They further suggest a new biosynthetic pathway in T. thermophilus, by which polyamines are formed from agmatine via N 1 -aminopropylagmatine. To confirm our speculation, we purified the expression product of the speB homolog and confirmed that the enzyme hydrolyzes N 1 -aminopropylagmatine to spermidine but does not act on agmatine.Polyamines play important roles in cell proliferation and cell differentiation. Common polyamines such as putrescine, spermidine, and spermine are distributed ubiquitously in cells and tissues at relatively high concentrations (1, 2).Thermus thermophilus, of which the genome project was completed using two strains, HB8 and HB27 (Structural-Biological Whole Cell Project at www.srg.harima.riken.go.jp/ thermus/j_index.htm and see Ref. 3, respectively), produces a variety of polyamines including unusually long polyamines and branched ones (4) (see Fig. 9C). These long and branched polyamines have a marked effect of protecting and stabilizing nucleic acids (5, 6) and of activating cell-free polypeptide synthesis at high temperature (7-9).In many organisms, such as bacteria, yeast, animals, and plants, the first step of polyamine biosynthesis is production of putrescine by decarboxylation of L-ornithine (see Fig. 9A). An additional or alternative pathway of putrescine biosynthesis that is often seen in plants and sometimes in bacteria is decarboxylation of L-arginine followed by hydrolysis of agmatine. Agmatine ureohydrolase or agmatinase, coded by the speB gene, catalyzes this second reaction. The next step is production of spermidine and spermine by the addition of an aminopropyl group to putrescine and spermidine, respectively. This reaction is catalyzed by spermidine or spermine synthase (putrescine/spermidine aminopropyltransferase) coded by the speE gene (1).To investigate the polyamine biosynthetic pathway in T. thermophilus, we constructed a disruption strain of the speB gene homolog of T. thermophilus. Disruption of the speB gene homolog resulted in drastic reduction of triamines, longer and branched polyamines without accumulation of agmatine, and in accumulation of an unknown compound. Double disruption of speB and speE gene homologs resulted in disappear...

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N1-Aminopropylagmatine, a New Polyamine Produced as a Key Intermediate in Polyamine Biosynthesis of an Extreme Thermophile, Thermus thermophilus

Ohnuma

Terui

Tamakoshi

et al. 2005

Journal of Biological Chemistry

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“…The polyamine biosynthetic and interconversion pathway in mammals is well established and has been described in multiple reviews (5,6). Putrescine is formed by ornithine decarboxylase (ODC), 2 and S-adenosylmethionine decarboxylase (AdoMetDC) produces dcAdoMet (Fig. 1).…”

Section: Polyamine Content and Metabolismmentioning

confidence: 99%

“…The importance of the effects on DNA stability is emphasized by the presence in acute thermophiles of high levels of polyamines, including branched chain molecules and longer linear amines than those found in mammals. These allow their survival at elevated temperatures (2). The majority of cellular polyamines are bound to RNA, and the changes in structure produced by binding to ribosomes, tRNA, and some mRNAs with particular sequences influence protein synthesis in multiple ways (3).…”

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Functions of Polyamines in Mammals

Pegg

2016

Journal of Biological Chemistry

514

428

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The content of spermidine and spermine in mammalian cells has important roles in protein and nucleic acid synthesis and structure, protection from oxidative damage, activity of ion channels, cell proliferation, differentiation, and apoptosis. Spermidine is essential for viability and acts as the precursor of hypusine, a post-translational addition to eIF5A allowing the translation of mRNAs encoding proteins containing polyproline tracts. Studies with Gy mice and human patients with the very rare X-linked genetic condition Snyder-Robinson syndrome that both lack spermine synthase show clearly that the correct spermine:spermidine ratio is critical for normal growth and development.There is very strong experimental evidence that maintenance of a normal polyamine content is essential for a wide variety of basic cellular functions. (a) Their content is very tightly controlled with the key enzymes in biosynthesis and interconversion having multiple levels of regulation in response to hormonal stimulation and polyamine content. (b) With the use of specific inhibitors of polyamine biosynthesis, it is relatively easy to substantially deplete cellular polyamine content, and striking effects have been observed on numerous critical cell functions including growth, differentiation, apoptosis, motility, and resistance to oxidative and other stresses. (c) The interaction of polyamines with nucleic acids and proteins can affect both structure and stability. Binding of polyamines to DNA affects its structure and stability (1). The importance of the effects on DNA stability is emphasized by the presence in acute thermophiles of high levels of polyamines, including branched chain molecules and longer linear amines than those found in mammals. These allow their survival at elevated temperatures (2). The majority of cellular polyamines are bound to RNA, and the changes in structure produced by binding to ribosomes, tRNA, and some mRNAs with particular sequences influence protein synthesis in multiple ways (3). Interactions of polyamines with proteins forming microtubules can influence their assembly and shape (4), and interaction with protein membrane receptors can have profound effects on crucial receptors.It should be stressed that these observations, although confirming that polyamines are essential cellular components, do not indicate that the polyamines necessarily play regulatory roles. Experimental support for such regulation would require the demonstration that physiological rather than pharmacological changes in polyamine content are associated with alterations in function, and this has rarely been demonstrated rigorously.It is not possible in a brief review to describe all of the actions that have been assigned to polyamines. The focus is on those functions that have been demonstrated to influence animal growth and development with particular emphasis on the phenotypes revealed by experimental animals and humans with an inborn error of metabolism leading to a reduction in spermine.

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“…18 In particular, they contribute to adaptation to various stresses including high-temperature conditions. 19 Agmatine is mainly generated by the decarboxylation of arginine, which is catalyzed by arginine decarboxylase (pdaD). Disruption of pdaD in the hyperthermophilic euryarchaeon, Thermococcus kodakaraensis, resulted in growth only in media supplemented with agmatine, 20 demonstrating that agmatine is an essential metabolite for this archaeon.…”

Section: Biogenesis Of 2-agmatinylcytidinementioning

confidence: 99%