Skip to main content
SpringerLink
Log in

Biosynthesis and production of quercitols and their application in the production of pharmaceuticals: current status and prospects

  • Mini-Review
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

A Correction to this article was published on 21 September 2018

This article has been updated

Abstract

(−)-vibo-Quercitol is a deoxyinositol (1l-1,2,4/3,5-cyclohexanepentol) that occurs naturally in low concentrations in oak species, honeydew honey, and Gymnema sylvestre. The author’s research group recently reported that (−)-vibo-quercitol and scyllo-quercitol (2-deoxy-myo-inositol, 1,3,5/2,4-cyclohexanepentol), a stereoisomer of (−)-vibo-quercitol, are stereoselectively synthesized from 2-deoxy-scyllo-inosose by the reductive reaction of a novel (−)-vibo-quercitol 1-dehydrogenase in Burkholderia terrae and of a known scyllo-inositol dehydrogenase in Bacillus subtilis, respectively. The author’s research group therefore identified two enzymes capable of producing both stereoisomers of deoxyinositols, which are rare in nature. (−)-vibo-Quercitol and scyllo-quercitol are potential intermediates for pharmaceuticals. In this review, the author describes the biosynthesis and enzymatic production of quercitols and myo-inositol stereoisomers and their application in the production of potential pharmaceuticals.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Change history

  • 21 September 2018

    The published online version contains mistake in the chemical structure of scyllo-inosose in Fig. 5 and Fig. 7. The correct configuration of 1-hydroxyl group in scyllo-inosose should have been the same to myo-inositol.

References

  • Anderson L (1972) The cyclitols. In: Pigman W, Horton D (eds) The carbohydrates, chemistry and biochemistry. Academic Press, London, pp 520–579

    Google Scholar 

  • Anderson WA, Magasanik B (1971) The pathway of myo-inositol degradation in Aerobacter aerogenes. Conversion of 2-deoxy-5-keto-d-gluconic acid to glycolytic intermediates. J Biol Chem 246:540–552

    Google Scholar 

  • Asano N, Kameda Y, Matsui K, Horii S, Fukase H (1990) Validamycin A, new pseudo-tetrasaccharide antibiotic. J Antibiot 43:1039–1041

    Article  CAS  Google Scholar 

  • Bates SH, Jones RB, Bailey CJ (2000) Insulin-like effect of pinitol. Br J Phramacol 130:1944–1948

    Article  CAS  Google Scholar 

  • Carlavilla D, Villamiel M, Martínez-Castro I, Moreno-Arribas V (2006) Occurrence and significance of quercitol and other inositols in wines during oak wood aging. Am J Enol Vitic 57:468–473

    CAS  Google Scholar 

  • Croze ML, Soulage CO (2013) Potential role and therapeutic interests of myo-inositol in metabolic diseases. Biochimie 95:1811–1827

    Article  CAS  Google Scholar 

  • Daniellou R, Phenix CP, Tam PH, Laliberte MC, Palmer DRJ (2005) Stereoselective oxidation of protected inositol derivatives catalyzed by inositol dehydrogenase from Bacillus subtilis. Org Biomol Chem 3:401–403

    Article  CAS  Google Scholar 

  • Dabhi AS, Bhatt NR, Shah MJ (2013) Voglibose: an alpha glucosidase inhibitor. J Clin Diagn Res 7:3023–3027

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dion HW, Woo PWK, Willmer NE, Kern DL, Onaga J, Fusari SA (1972) Butirosin, a new aminoglycosidic antibiotic complex: isolation and characterization. Antimicrob Ag Chemther 2:84–88

    Article  CAS  Google Scholar 

  • Horii S, Fukase H, Kameda Y (1985) Stereoselective conversion of valienamine and validamine into valiolamine. Carbohydr Res 140:185–200

    Article  CAS  Google Scholar 

  • Itoh N, Isotani K, Nakamura M, Inoue K, Isogai Y, Makino Y (2012) Efficient synthesis of optically pure alcohols by asymmetric hydrogen-transfer biocatalysis: application of engineered enzymes in a 2-propanol-water medium. Appl Microbiol Biotechnol 93:1075–1085

    Article  CAS  Google Scholar 

  • Itoh N, Kurokawa J, Toda H, Konishi K (2017) Identification and characterization of a novel (−)-vibo-quercitol 1-dehydrogenase from Burkholderia terrae suitable for production of (−)-vibo-quercitol from 2-deoxy-scyllo-inosose. Appl Microbiol Biotechnol 101:7545–7555

    Article  CAS  Google Scholar 

  • Iuorno MJ, Jakubowicz DJ, Baillargeon JP, Dillon P, Gunn RD, Allan G, Nestler JE (2002) Effects of d-chiro-inositol in lean women with the polycystic ovary syndrome. Endocr Pract 8:417–423

    Article  Google Scholar 

  • Jiang G, Krishnan HA, Kim YW, Wacek TJ, Krishnan HB (2001) A functional myo-inositol dehydrogenase gene is required for efficient nitrogen fixation and competitiveness of Sinorhizobium fredii USDA191 to nodulate soybean (Glycine max [L.] Merr.). J Bacteriol 183:2595–2604

    Article  CAS  Google Scholar 

  • Kakinuma K, Nango E, Kudo F, Matsushima Y, Eguchi T (2000) An expeditious chemo-enzymatic route from glucose to catechol by the use of 2-deoxy-scyllo-inosose synthase. Tetrahedron Lett 41:1935–1938

    Article  CAS  Google Scholar 

  • Kogure T, Wakisaka N, Takaku H, Takagi M (2007) Efficient production of 2-deoxy-scyllo-inosose from d-glucose by metabolically engineered Escherichia coli. J Biotechnol 129:502–509

    Article  CAS  Google Scholar 

  • Kohler PRA, Zheng JY, Schoffers E, Rossbach S (2010) Inositol catabolism, a key pathway in Sinorhizobium meliloti for competitive host nodulation. Appl Environ Microbiol 76:7972–7980

    Article  CAS  Google Scholar 

  • Kudo F, Numakura M, Tamegai H, Yamamoto H, Eguchi T, Kakinuma K (2005) Extended sequence and functional analysis of the butirosin biosynthetic gene cluster in Bacillus circulans SANK 72073. J Antibiot 58:373–379

    Article  CAS  Google Scholar 

  • Kuno S, Takahashi A, Ogawa S (2011) Transformation of quercitols into 4-methylenecyclohex-5-ene-1,2,3-triol derivatives, precursors for the chemical chaperones N-octyl-4-epi-β-valienamine (NOEV) and N-octyl-β-valienamine (NOV). Bioorg Med Chem Lett 21:7185–7188

    Article  Google Scholar 

  • Lee D, Lee WS, Lim S, Kim YK, Jung HY, Das S, Lee J, Luo W, Kim KT, Chung SK (2017) A guanidine-appended scyllo-inositol derivative AAD-66 enhances brain delivery and ameliorates Alzheimer’s phenotypes. Sci Rep https://www.ncbi.nlm.nih.gov/pubmed/2907487 7(14125)

  • Loewus FA, Murthy PPN (2000) myo-Inositol metabolism in plants. Plant Sci 150:1–19

    Article  CAS  Google Scholar 

  • Ma K, Thomason LA, McLaurin J (2012) scyllo-Inositol, preclinical, and clinical data for Alzheimer’s disease. Adv Pharmacol 64:177–212

    Article  CAS  Google Scholar 

  • Majumder AL, Johnson MD, Henry SA (1997) 1l-myo-Inositol-1-phosphate synthase. Biochim Biophys Acta 1348:245–256

    Article  CAS  Google Scholar 

  • Morinaga T, Ashida H, Yoshida K (2010) Identification of two scyllo-inositol dehydrogenases in Bacillus subtilis. Microbiol 156:1538–1546

    Article  CAS  Google Scholar 

  • Miyazawa D, Matsumoto K (2015) Method for producing 2-deoxy-scyllo-inosose. Patent application WO2015005451 A1 (PCT/JP2014/068497).

    Google Scholar 

  • Ogawa S, Kanto M (2007) Synthesis of valiolamine and some precursors for bioactive carbaglycosylamines from (−)-vibo-quercitol produced by biogenesis of myo-inositol. J Nat Prod 70:493–497

    Article  CAS  Google Scholar 

  • Ogawa S, Uetsuki S, Tezuka Y, Morikawa T, Takahashi A, Sato K (1999) Synthesis and evaluation of glucocerebrosidase inhibitory activity of anhydro deoxyinositols from (+)-epi- and (−)-vibo-quercitols. Bioorg Med Chem Lett 9:1493–1498

    Article  CAS  Google Scholar 

  • Ota Y, Tamegai H, Kudo F, Kuriki H, Koike-Takeshita A, Eguchi T, Kakinuma K (2000) Butirosin-biosynthetic gene cluster from Bacillus circulans. J Antibiot 53:1158–1167

    Article  CAS  Google Scholar 

  • Potawale SE, Shinde VM, Anandi L, Borade S, Dhalawat H, Deshmukh RS (2008) Gymnema sylvestre: a comprehensive review. Pharmacol Online 2:144–157

    Google Scholar 

  • Ramaley R, Fujita Y, Freese E (1979) Purification and properties of Bacillus subtilis inositol dehydrogenase. J Biol Chem 254:7684–7690

    CAS  PubMed  Google Scholar 

  • Roscales S, and Plumet J (2016) Biosynthesis and biological activity of carbasugars. Int J Carbohydr Chem ID4760548

  • Sanz ML, Sanz J, Martínez-Castro I (2004) Presence of some cyclitols in honey. Food Chem 84:133–135

    Article  CAS  Google Scholar 

  • Schlemmer U, Frølich W, Prieto RM, Grases F (2009) Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis. Mol Nutr Food Res 53:S330–S375

    Article  Google Scholar 

  • Serit M, Okubo T, Su RH, Hagiwara N, Kim M, Iwagata T, Yamamoto T (1991) Antibacterial compounds from oak, Quercus acuta Thunb. Agric Biol Chem 55:19–23

    Article  CAS  Google Scholar 

  • Stein AJ, Geiger JH (2002) The crystal structure and mechanism of 1-l-myo-inositol-1-phosphate synthase. J Biol Chem 277:9484–9491

    Article  CAS  Google Scholar 

  • Takahashi A, Kanbe K, Tamamura T, Sato K (1999) Bioconversion of myo-inositol to rare cyclic sugar alcohols. Anticancer Res 19:3807

    Google Scholar 

  • Takeuchi M, Takai N, Asano N, Kameda Y, Matsui K (1990) Inhibitory effect of validamine, valienamine and valiolamine on activities of carbohydrases in rat small intestinal brush border membranes. Chem Pharm Bull (Tokyo) 38:1970–1972

    Article  CAS  Google Scholar 

  • Walker JB (1975) myo-Inositol: NAD+ 2-oxidoreductase. In: Hash JH (ed) Methods in enzymology, vol 43. Academic Press, London, pp 433–439

    Google Scholar 

  • Wacharasindhu S, Worawalai W, Rungprom W, Phuwapraisirisan P (2009) (+)-proto-Quercitol, a natural versatile chiral building block for the synthesis of the α-glucosidase inhibitors, 5-amino-1,2,3,4-cyclohexanetetrols. Tetrahedron Lett 50:2189–2192

    Article  CAS  Google Scholar 

  • Yamaoka M, Osawa S, Morinaga T, Takenaka S, Yoshida K (2011) A cell factory of Bacillus subtilis engineered for the simple bioconversion of myo-inositol to scyllo-inositol, a potential therapeutic agent for Alzheimer’s disease. Microb Cell Factories 10:69

    Article  CAS  Google Scholar 

  • Yamauchi N, Kakinuma K (1995) Enzymic carbocycle formation in microbial secondary metabolism. The mechanism of the 2-deoxy-scyllo-inosose synthase reaction as a crucial step in the 2-deoxystreptamine biosynthesis in Streptomyces fradiae. J Org Chem 60:5614–5619

    Article  CAS  Google Scholar 

  • Yebra MJ, Zúniga M, Beaufils S, Perez-Martínez G, Deutscher J, Monedero V (2007) Identification of a gene cluster enabling Lactobacillus casei BL23 to utilize myo-inositol. Appl Environ Microbiol 73:3850–3858

    Article  CAS  Google Scholar 

  • Yoshida K, Yamaguchi M, Morinaga T, Kinehara M, Ikeuchi M, Kinehara M, Ashida H (2006) Genetic modification of Bacillus subtilis for production of d-chiro-inositol, an investigational drug candidate for treatment of type 2 diabetes and polycystic ovary syndrome. Appl Environ Microbiol 72:1310–1315

    Article  CAS  Google Scholar 

  • Yoshida K, Yamaguchi M, Morinaga T, Kinehara M, Ikeuchi M, Ashida H, Fujita Y (2008) myo-Inositol catabolism in Bacillus subtilis. J Biol Chem 283:10415–10424

    Article  CAS  Google Scholar 

  • Yoshida K, Sanbongi A, Murakami A, Suzuki H, Takenaka S, Takami H (2012) Three inositol dehydrogenases involved in utilization and interconversion of inositol stereoisomers in a thermophile, Geobacillus kaustophilus HTA426. Microbiology 158:1942–1952

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama, 939-0398, Japan

    Nobuya Itoh

Authors
  1. Nobuya Itoh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nobuya Itoh.

Ethics declarations

Conflict of interest

The author declares that he has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by the author.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Itoh, N. Biosynthesis and production of quercitols and their application in the production of pharmaceuticals: current status and prospects. Appl Microbiol Biotechnol 102, 4641–4651 (2018). https://doi.org/10.1007/s00253-018-8972-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-018-8972-y

Keywords

Search

Navigation