Genetic Modification of
            <i>Bacillus subtilis</i>
            for Production of
            <scp>d</scp>
            -
            <i>chiro</i>
            -Inositol, an Investigational Drug Candidate for Treatment of Type 2 Diabetes and Polycystic Ovary Syndrome

Yoshida, Ken-ichi; Yamaguchi, Masanori; Morinaga, Tetsuro; Ikeuchi, Maya; Kinehara, Masaki; Ashida, Hitoshi

doi:10.1128/aem.72.2.1310-1315.2006

Cited by 55 publications

(56 citation statements)

References 21 publications

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“…myo-inositol, can change accumulation of other soluble carbohydrates, particularly RFOs and modify tolerance of grains and seedlings to abiotic stresses. On the other hand, D-pinitol and D-chiro-inositol indicate some health benefits both cyclitols and their galactosides can be helpful compounds in treatment of type 2 diabetes (lowering glucose level in blood), polycystic ovary syndrome (Yoshida et al 2006), and Alzheimers disease (Nitz et al 2008). Pinitol also possesses anti-inflammatory (Sethi et al 2008) and anti-viral properties (Zhan et al 2006) and has been implicated in the prevention of cardiovascular diseases (Choi et al 2009).…”

Section: Introductionmentioning

confidence: 99%

Cyclitols in maturing grains of wheat, triticale and barley

Lahuta

Goszczyńska

2011

Acta Soc Bot Pol

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In the present study, the feeding of stem-flag leaf-ear explants of wheat, triticale and barley with D-chiro-inositol and D-pinitol was used for modification of the composition of soluble carbohydrates in grains without genetic transformation of plants. Maturing grains indicated ability to uptake exogenously applied cyclitols, not occurring naturally in cereal plants, and synthesized their α-D-galactosides. The pattern of changes in soluble carbohydrates during grain maturation and germination was not disturbed by the uptake and accumulation of cyclitols. Both, D--chiro-inositol and D-pinitol as well as their α-D-galactosides can be an additional pool of soluble carbohydrates accumulated by maturing grains, without decreasing seeds viability. This is the first report indicating the possibility of introduction of cyclitols with potentially human health benefits properties into cereal grains.

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Section: Introductionmentioning

confidence: 99%

Cyclitols in maturing grains of wheat, triticale and barley

Lahuta

Goszczyńska

2011

Acta Soc Bot Pol

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“…Recently IolG was also shown to be able to act on D-chiro-inositol (DCI, compound [2]) to yield 1-keto-DCI (compound [4]), and IolI interconverts 1-keto-DCI and 2KMI, indicating that not only MI but also DCI is metabolized through the MI catabolic pathway ( Fig. 1) (14). In addition, pinitol (3-Omethyl-DCI) contained in soybean appeared to be an alternative substrate of IolG, and this substrate was degraded depending on the presence of functional iol genes (15).…”

mentioning

confidence: 99%

“…IolH is paralogous to both IolI and IolE. The iolI gene product was shown to be 2KMI/1-keto-DCI isomerase involved in DCI metabolism (14), and IolE is known as 2KMI dehydratase indispensable for MI catabolism (13). This suggests that IolH may also act on a certain ketose as its isomerase or dehydratase.…”

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confidence: 99%

myo-Inositol Catabolism in Bacillus subtilis

Yoshida

Yamaguchi

Morinaga

et al. 2008

Journal of Biological Chemistry

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116

130

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The iolABCDEFGHIJ operon of Bacillus subtilis is responsible for myo-inositol catabolism involving multiple and stepwise reactions. Previous studies demonstrated that IolG and IolE are the enzymes for the first and second reactions, namely dehydrogenation of myo-inositol to give 2-keto-myo-inositol and the subsequent dehydration to 3D-(3,5/4)-trihydroxycyclohexane-1,2-dione. In the present studies the third reaction was shown to be the hydrolysis of 3D-(3,5/4)-trihydroxycyclohexane-1,2-dione catalyzed by IolD to yield 5-deoxy-D-glucuronic acid. The fourth reaction was the isomerization of 5-deoxy-D-glucuronic acid by IolB to produce 2-deoxy-5-keto-D-gluconic acid. Next, in the fifth reaction 2-deoxy-5-keto-D-gluconic acid was phosphorylated by IolC kinase to yield 2-deoxy-5-keto-D-gluconic acid 6-phosphate. IolR is known as the repressor controlling transcription of the iol operon. In this reaction 2-deoxy-5-keto-Dgluconic acid 6-phosphate appeared to be the intermediate acting as inducer by antagonizing DNA binding of IolR. Finally, IolJ turned out to be the specific aldolase for the sixth reaction, the cleavage of 2-deoxy-5-keto-D-gluconic acid 6-phosphate into dihydroxyacetone phosphate and malonic semialdehyde. The former is a known glycolytic intermediate, and the latter was previously shown to be converted to acetyl-CoA and CO 2 by a reaction catalyzed by IolA. The net result of the inositol catabolic pathway in B. subtilis is, thus, the conversion of myo-inositol to an equimolar mixture of dihydroxyacetone phosphate, acetyl-CoA, and CO 2 . myo-Inositol (MI)2 is abundant in soil and also common and essential in plants and animals. A number of microorganisms, including Bacillus subtilis (1), Cryptococcus melibiose (2), Aerobacter aerogenes (reclassified as Enterobacter aerogenes/Klebsiella mobilis) (3), Rhizobium leguminosarum bv. viciae (4), Sinorhizobium meliloti (5), Sinorhizobium fredii (6), Corynebacterium glutamicum (7), and Lactobacillus casei (8) can grow on MI as the sole carbon source. MI catabolism in A. aerogenes was studied biochemically, and a pathway of the catabolism finally yielding acetyl-CoA and dihydroxyacetone phosphate (DHAP) was proposed (9). However, our knowledge of the molecular genetics of bacterial MI catabolism has been restricted to B. subtilis (1, 10 -12). In B. subtilis, the iol divergon, comprising the operons iolABCDEFGHIJ and iolRS (1), and the iolT gene (12) were shown to be required for inositol catabolism (Fig. 1). Nowadays, a large number of bacteria have genes annotated iol in their genome sequence, but the annotation is only based on sequence similarity to B. subtilis iol genes, as relatively few studies have been done to demonstrate the participation of the deduced iol genes in MI catabolism.In B. subtilis, a repressor encoded by iolR is responsible for the regulation of all the iol genes (11, 12). In the absence of MI in the growth medium, the IolR repressor binds to the operator site within the promoter regions to repress the transcription. In its presence, howev...

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“…In B. subtilis, the iol genes are involved in metabolism not only of myo-inositol but also of pinitol and D-chiro-inositol. 30,31) In addition, the iol genes are induced in the presence of each of these compounds. We characterized S. fredii USDA191 iolE encoding 2-ketomyo-inositol dehydratase specific for the second step in the reaction in the myo-inositol catabolic pathway, suggesting that USDA191 might possess a pathway analogous to that of B. subtilis.…”

Section: Cloning and Nucleotide Sequencing Of S Fredii Usda191 Iole mentioning

confidence: 99%