Skip to main content
SpringerLink
Log in

White biotechnology for green chemistry: fermentative 2-oxocarboxylic acids as novel building blocks for subsequent chemical syntheses

  • Environmental Biotechnology
  • Published:
Journal of Industrial Microbiology and Biotechnology

Abstract

Functionalized compounds, which are difficult to produce by classical chemical synthesis, are of special interest as biotechnologically available targets. They represent useful building blocks for subsequent organic syntheses, wherein they can undergo stereoselective or regioselective reactions. “White Biotechnology” (as defined by the European Chemical Industry [http://www.europabio.org/white_biotech.htm], as part of a sustainable “Green Chemistry,”) supports new applications of chemicals produced via biotechnology. Environmental aspects of this interdisciplinary combination include:

  • Use of renewable feedstock

  • Optimization of biotechnological processes by means of:

    • New “high performance” microorganisms

    • On-line measurement of substrates and products in bioreactors

    • Alternative product isolation, resulting in higher yields, and lower energy demand

In this overview we describe biotechnologically produced pyruvic, 2-oxopentaric and 2-oxohexaric acids as promising new building blocks for synthetic chemistry. In the first part, the microbial formation of 2-oxocarboxylic acids (2-OCAs) in general, and optimization of the fermentation steps required to form pyruvic acid, 2-oxoglutaric acid, and 2-oxo-d-gluconic acid are described, highlighting the fundamental advantages in comparison to chemical syntheses. In the second part, a set of chemical formula schemes demonstrate that 2-OCAs are applicable as building blocks in the chemical synthesis of, e.g., hydrophilic triazines, spiro-connected heterocycles, benzotriazines, and pyranoic amino acids. Finally, some perspectives are discussed.

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
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13

Similar content being viewed by others

References

  1. Anastas PT, Warner JC (1998) Green chemistry: theory and practice. Oxford University Press, Oxford, pp 1–152

    Google Scholar 

  2. Andersch J, Sicker D (1999) Reductive cyclization of carbohydrate 2-nitrophenyl-hydrazones to chiral functionalized 1,2,4-benzotriazines and benzimidazoles. J Heterocycl Chem 36:589–594

    CAS  Google Scholar 

  3. Andersch J, Sicker D, Wilde H (1999) Synthesis of spiro[1,4-benzothiazin-2,2′-pyrans] starting from methyl D-arabino-2-hexulosonate. J Heterocycl Chem 36:457–460

    CAS  Google Scholar 

  4. Andersch J, Sicker D, Wilde H (1999) Synthesis of spiro[pyrido[3,2-b][1,4]oxazin-2,2′-pyrans] based upon methyl d-arabino-2-hexulosonate. J Heterocycl Chem 40:57–58

    Google Scholar 

  5. Andersch J, Sicker D, Wilde H (1999) Methyl d-arabino-hex-2-ulosonate as a building block for spiro[1,4-benzoxazine-2,2′-pyrans]. Carbohydr Res 316:85–94

    Article  CAS  Google Scholar 

  6. Andersch J, Sicker D, Wilde H (1999) Synthesis of spiro[pyrido[3,2-b][oxazin-2,2′-pyrans] based upon methyl d-arabino-2-hexulopyranosonate. Tetrahedron Lett 40:57–58

    Article  Google Scholar 

  7. Andersch J, Hennig H, Wilde H (2000) N-Glycosidation of d-arabino-Hex-2-ulosonic acid. Carbohydr Res 329:693–696

    Article  PubMed  CAS  Google Scholar 

  8. Anton DL, Dicosimo R, Witterholt VG (1995) Process for the preparation of pyruvic acid. WO9500656 DuPont (US)

  9. Aurich A, Stottmeister U, Weißbrodt E, Wilde H, Sicker D, Andersch J (2000) Microbiologically produced 2-oxocarboxylic acids: new possibilities in organic synthesis. Abstracts of 19th annual DECHEMA-meeting of biotechnologists. Leipzig, p 203

  10. Blitzke T, Hartenstein H, Sicker H, Wilde H (1993) Synthesen auf der Basis von Oxoglutarsäure, III. Synthese und Reaktionen von (E)-2-Oxoglutaconsäuredimethylester. J Prakt Chem 335:683–686

    Article  CAS  Google Scholar 

  11. Blitzke T, Greif R, Kempe M, Pink M, Pulst D, Sicker D, Wilde H (1994) Organic synthesis based on 2-oxoglutaric acid, IV. Regioselective synthesis of substituted 2-(2-Methoxycarbonyl-2 H-thiopyran-3-yl) glyoxylic acid methylester (in German). J Prakt Chem 336:136–165

    Article  Google Scholar 

  12. Blitzke T, Sicker D, Wilde H (1997) Organic syntheses based on 2-oxoglutaric acid V. Syntheses of novel 2 H-1,4-benzothiazines and a 2,5-dihydro-1,5-benzothiazepine. J Heterocycl Chem 34:453–455

    CAS  Google Scholar 

  13. Chernyavskaya OG, Shishkanova NV, Finogenova TV (1997) Biosynthesis of alpha-ketoglutaric acid from ethanol by yeasts. Appl Biochem Microbiol 33:261–265

    Google Scholar 

  14. Cooper AJL, Ginos JZ, Meister A (1983) Synthesis and properties of the α-keto acids. Chem Rev 83:321–358

    Article  CAS  Google Scholar 

  15. Cooper B (1988) Microbial manufacture of pyruvic acid from d-(−)-lactate, EP-A 0313850, BASF

  16. Crawford TC, Andrews GC, Faubl H, Chmurny GN (1980) The structure of biologically important carbohydrates. A carbon-13 nuclear magnetic resonance study of tautomeric equilibriums in several hexulosonic acids and related compounds. J Am Chem Soc 102:2220–2225

    Article  CAS  Google Scholar 

  17. Hanselmann KW (1982) Lignochemicals. Experientia 38:176–189

    Article  CAS  Google Scholar 

  18. Hartenstein H, Blitzke T, Sicker H, Wilde H (1993) Synthesen auf der Basis von 2-Oxoglutarsäure, II. Zur Synthese von Heterocyclen durch Reaktionen von 3-Brom-2-Oxoglutarsäuredimethylester mit Binucleophilen. J Prakt Chem 335:176–180

    Article  CAS  Google Scholar 

  19. Hiroyuki N, Hideaki M, Masao S, Masaya M, Noriyuki Y (2004) Preparation of 2-ketocarboxylic acid from carbon dioxide. US 2004009565

  20. Illchenko AP, Chernyavskaya NV, Shishkanova NV, Finogenova TV (2003) Biochemical characterisation of the yeast Yarrowia lipolytica overproducing carboxylic acids from ethanol. Mikrobiology 72:418–422

    Google Scholar 

  21. Izumi Y, Matsumura Y, Tani Y, Yamada H (1982) Pyruvic acid production from 1,2-propanediol by thiamine requiring Acinetobacter. Agric Biol Chem 46:2673–2679

    CAS  Google Scholar 

  22. Khodja M, Schwesinger H, Sicker D, Wilde H (1994) Synthesis of 3,4-dihydro-pyridazino[1,6-a]benzimidazoles by reductive cyclization of dialkyl 2-(2-nitrophenyl-hydrazono) glutarates. Heterocycles 37:401–411

    Article  CAS  Google Scholar 

  23. Kirrbach S, Schnelle RR, Stottmeister U, Hauptmann S, Mann G, Wilde H, Sicker D (1992) Optimierte Synthesen für Methyl- und Natrium-2-oxo-d-gluconat als Synthesebausteine. J Prakt Chem 334:537–539

    Article  CAS  Google Scholar 

  24. Klingler FD, Ebertz W (2003) Oxocarboxylic acids. In: Ullmann’s Encyclopedia of industrial chemistry, 6th edn, vol 24. Wiley-VCH, Weinheim, pp 545–552

  25. Li Y, Chen J, Lun S-Y (2001) Biotechnological production of pyruvic acid. Appl Microbiol Biotechnol 57:451–459

    Article  PubMed  CAS  Google Scholar 

  26. Li Y, Chen J, Lun SY, Rui XS (2001) Efficient pyruvate production by a multi vitamin auxotroph of Troulopsi glabrata: key role and optimisation of vitamin level. J Biotechnol 81:27–34

    Article  Google Scholar 

  27. Maldonado P, Desmarquest J-P, Gaillardin C, Binet D (1973) Process for getting diploid Candida lipolytica strains for alpha-ketoglutarate fermentation, US 3930946 (Institute Francaise du Petrole 1973)

  28. Mamoru S, Motomu O (2003) Method for producing pyruvic acid, JP2003146935 (Mitsubishi Rayon Co. Ltd.)

  29. Mattioda G, Christidis Y (2003) In: Ullmann’s encyclopedia of industrial chemistry, 6th edn, vol 16. Wiley-VCH, Weinheim, pp 697–700

  30. Merck Co. (1956) Improvements in or relating to cyclic nitrogen compounds. GB 755036 (Prior. US 1953)

  31. Misenheimer TJ, Anderson RT, Lagoda AA, Tyler DD (1965) Production of 2-keto-gluconic acid by Serratia marcescens. Appl Microbiol 13:393–396

    PubMed  CAS  Google Scholar 

  32. Miyata R, Tsutsui H, Yonehara T (1989) Manufacture of pyruvic acid with amino-oxyacetic acid resistant Torulopsis sp. Jpn Patent 0155186

  33. Miyata R, Tsutsui H, Yonehara T (1990) Method for producing pyruvic acid by fermentation. US patent 4971907

  34. Miyata R, Yonehara T (1996) Improvement of fermentative production of pyruvate from glucose by Torulopsis glabrata, IFO 0005. J Ferment Bioeng 82:475–479

    Article  CAS  Google Scholar 

  35. Miyata R, Yonehara T (1999) Breeding of high pyruvate producing Torulopsis galabrata with acquired reduced pyruvate decarboxylase. J Biosci Bioeng 88:173–178

    Article  PubMed  CAS  Google Scholar 

  36. Morgunov IG, Kamzolova SV, Perevoznikova OA, Shishkanova NV, Finogenova TV (2004) Pyruvic acid production by a thiamine auxotroph of Yarrowia lipolytica. Process Biochem 39:1469–1474

    Article  CAS  Google Scholar 

  37. Schwesinger H, Dalski A, Sicker D, Wilde H, Mann G (1992) Synthesen auf der Basis von 2-Oxoglutarsäure. I. Synthese substituierter 2-Nitrophenylhydrazone von 2-Oxodicarbonsäureestern und Untersuchung ihres Tautomerie- und Absorptionsverhaltens. J Prakt Chem 334:257–264

    Article  CAS  Google Scholar 

  38. Shaban MAE, Taha MAM, Hamouda HMA (1998) Synthesis and antimicrobial activities of condensed and uncondensed 1,2,4-triazines. Heterocycl Commun 4:351–359

    CAS  Google Scholar 

  39. Smits PCC (1986) Process for the preparation of 2-ketoaldonic acids, US 4620034, Akzo (1985)

  40. Stottmeister U, Puschendorf K, Thiersch A, Berger R, Düresch R et al (1988) Verfahren zur Gewinnung von 2-Oxogluconsäure mittels Bakterien. Patent DD 278 362 A1 IBT/UFZ

  41. Stottmeister U, Schoenfelder M, Wilde H, Sicker D, Andersch J (2001) Novel substituted 1,2,4-benzotriazine. A method for their production and the use thereof. WO01/46162 A2

  42. Stubbs JJ, Lockwood LB, Roe ET, Tabenkin B, Ward GE (1940) Ketogluconic acid from glucose. Ind Eng Chem 32:1626–1631

    Article  CAS  Google Scholar 

  43. Tabaka K, Kimura K, Yamaguchi Y (1969) Process for producing L-glutamic acid and alpha-ketoglutaric acid, US 3450599 Kyowa Hakko Kogyo 1964

  44. Tsugawa R, Nakase T, Yamashita K (1969) Production of alpha-ketoglutaric acid by fermentation of hydrocarbons, US 3616213 (Ajinomoto 1968)

  45. Wang Q, He P, Lu D, Shen A, Jiang N (2002) Screening on pyruvate producing yeasts. Lett Appl Microbiol 35:338–342

    Article  PubMed  CAS  Google Scholar 

  46. Weissbrodt E, Barth G, Weber H, Stottmeister U, Düresch R, Richter P (1988) Production of 2-oxoglutaric acid by yeasts, DD 267 999 IBT/ UFZ

  47. http://www.biorenew.iastate.edu/Biowa Bioeconomy initiative

  48. http://www.chemicalvision2020.org/pdfs/direct_capture.pdf

  49. http://www.europabio.org/white_biotech.htm

  50. http://www.extension.iastate.edu/Pages/valag/vaaforum03/visionforiowa.ppt

  51. http://www.vogelbusch.com

Download references

Author information

Authors and Affiliations

  1. Department of Environmental Biotechnology, UFZ Center for Environmental Research, Permoserstraße 15, 04318, Leipzig, Germany

    U. Stottmeister & A. Aurich

  2. Institute of Organic Chemistry, University of Leipzig, Johannisallee 29, 04103, Leipzig, Germany

    H. Wilde, J. Andersch, S. Schmidt & D. Sicker

Authors
  1. U. Stottmeister
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Aurich
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. Wilde
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. Andersch
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. Schmidt
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D. Sicker
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to U. Stottmeister.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stottmeister, U., Aurich, A., Wilde, H. et al. White biotechnology for green chemistry: fermentative 2-oxocarboxylic acids as novel building blocks for subsequent chemical syntheses. J IND MICROBIOL BIOTECHNOL 32, 651–664 (2005). https://doi.org/10.1007/s10295-005-0254-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10295-005-0254-x

Keywords

Search

Navigation