Microbiologically produced carboxylic acids used as building blocks in organic synthesis

Research output: Contribution to journalReview articleResearchpeer review

Authors

  • Andreas Aurich
  • Robert Specht
  • Roland A Müller
  • Ulrich Stottmeister
  • Venelina Yovkova
  • Christina Otto
  • Martina Holz
  • Gerold Barth
  • Philipp Heretsch
  • Franziska A Thomas
  • Dieter Sicker
  • Athanassios Giannis

Research Organisations

External Research Organisations

  • Helmholtz Centre for Environmental Research (UFZ)
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Details

Original languageEnglish
Pages (from-to)391-423
Number of pages33
JournalSubcellular Biochemistry
Volume64
Publication statusPublished - 2012

Abstract

Oxo- and hydroxy-carboxylic acids are of special interest in organic synthesis. However, their introduction by chemical reactions tends to be troublesome especially with regard to stereoselectivity. We describe herein the biotechnological preparation of selected oxo- and hydroxycarboxylic acids under "green" conditions and their use as promising new building blocks. Thereby, our biotechnological goal was the development of process fundamentals regarding the variable use of renewable raw materials, the development of a multi purpose bioreactor and application of a pilot plant with standard equipment for organic acid production to minimize the technological effort. Furthermore the development of new product isolation procedures, with the aim of direct product recovery, capture of products or single step operation, was necessary. The application of robust and approved microorganisms, also genetically modified, capable of using a wide range of substrates as well as producing a large spectrum of products, was of special importance. Microbiologically produced acids, like 2-oxo-glutaric acid and 2-oxo-D-gluconic acid, are useful educts for the chemical synthesis of hydrophilic triazines, spiro-connected heterocycles, benzotriazines, and pyranoic amino acids. The chiral intermediate of the tricarboxylic acid cycle, (2R,3S)-isocitric acid, is another promising compound. For the first time our process provides large quantities of enantiopure trimethyl (2R,3S)-isocitrate which was used in subsequent chemical transformations to provide new chiral entities for further usage in total synthesis and pharmaceutical research.Oxo- and hydroxy-carboxylic acids are of special interest in organic synthesis. However, their introduction by chemical reactions tends to be troublesome especially with regard to stereoselectivity. We describe herein the biotechnological preparation of selected oxo- and hydroxycarboxylic acids under "green" conditions and their use as promising new building blocks. Thereby, our biotechnological goal was the development of process fundamentals regarding the variable use of renewable raw materials, the development of a multi purpose bioreactor and application of a pilot plant with standard equipment for organic acid production to minimize the technological effort. Furthermore the development of new product isolation procedures, with the aim of direct product recovery, capture of products or single step operation, was necessary. The application of robust and approved microorganisms, also genetically modified, capable of using a wide range of substrates as well as producing a large spectrum of products, was of special importance. Microbiologically produced acids, like 2-oxo-glutaric acid and 2-oxo-D-gluconic acid, are useful educts for the chemical synthesis of hydrophilic triazines, spiro-connected heterocycles, benzotriazines, and pyranoic amino acids. The chiral intermediate of the tricarboxylic acid cycle, (2R,3S)-isocitric acid, is another promising compound. For the first time our process provides large quantities of enantiopure trimethyl (2R,3S)-isocitrate which was used in subsequent chemical transformations to provide new chiral entities for further usage in total synthesis and pharmaceutical research.

Keywords

    Carboxylic Acids/metabolism, Chemistry Techniques, Synthetic/methods, Gluconates/metabolism, Isocitrates/metabolism, Ketoglutaric Acids/metabolism, Metabolic Engineering/methods, Microbiological Phenomena/genetics, Yarrowia/genetics

Sustainable Development Goals

Cite this

Microbiologically produced carboxylic acids used as building blocks in organic synthesis. / Aurich, Andreas; Specht, Robert; Müller, Roland A et al.
In: Subcellular Biochemistry, Vol. 64, 2012, p. 391-423.

Research output: Contribution to journalReview articleResearchpeer review

Aurich, A, Specht, R, Müller, RA, Stottmeister, U, Yovkova, V, Otto, C, Holz, M, Barth, G, Heretsch, P, Thomas, FA, Sicker, D & Giannis, A 2012, 'Microbiologically produced carboxylic acids used as building blocks in organic synthesis', Subcellular Biochemistry, vol. 64, pp. 391-423. https://doi.org/10.1007/978-94-007-5055-5_19
Aurich, A., Specht, R., Müller, R. A., Stottmeister, U., Yovkova, V., Otto, C., Holz, M., Barth, G., Heretsch, P., Thomas, F. A., Sicker, D., & Giannis, A. (2012). Microbiologically produced carboxylic acids used as building blocks in organic synthesis. Subcellular Biochemistry, 64, 391-423. https://doi.org/10.1007/978-94-007-5055-5_19
Aurich A, Specht R, Müller RA, Stottmeister U, Yovkova V, Otto C et al. Microbiologically produced carboxylic acids used as building blocks in organic synthesis. Subcellular Biochemistry. 2012;64:391-423. doi: 10.1007/978-94-007-5055-5_19
Aurich, Andreas ; Specht, Robert ; Müller, Roland A et al. / Microbiologically produced carboxylic acids used as building blocks in organic synthesis. In: Subcellular Biochemistry. 2012 ; Vol. 64. pp. 391-423.
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TY - JOUR

T1 - Microbiologically produced carboxylic acids used as building blocks in organic synthesis

AU - Aurich, Andreas

AU - Specht, Robert

AU - Müller, Roland A

AU - Stottmeister, Ulrich

AU - Yovkova, Venelina

AU - Otto, Christina

AU - Holz, Martina

AU - Barth, Gerold

AU - Heretsch, Philipp

AU - Thomas, Franziska A

AU - Sicker, Dieter

AU - Giannis, Athanassios

PY - 2012

Y1 - 2012

N2 - Oxo- and hydroxy-carboxylic acids are of special interest in organic synthesis. However, their introduction by chemical reactions tends to be troublesome especially with regard to stereoselectivity. We describe herein the biotechnological preparation of selected oxo- and hydroxycarboxylic acids under "green" conditions and their use as promising new building blocks. Thereby, our biotechnological goal was the development of process fundamentals regarding the variable use of renewable raw materials, the development of a multi purpose bioreactor and application of a pilot plant with standard equipment for organic acid production to minimize the technological effort. Furthermore the development of new product isolation procedures, with the aim of direct product recovery, capture of products or single step operation, was necessary. The application of robust and approved microorganisms, also genetically modified, capable of using a wide range of substrates as well as producing a large spectrum of products, was of special importance. Microbiologically produced acids, like 2-oxo-glutaric acid and 2-oxo-D-gluconic acid, are useful educts for the chemical synthesis of hydrophilic triazines, spiro-connected heterocycles, benzotriazines, and pyranoic amino acids. The chiral intermediate of the tricarboxylic acid cycle, (2R,3S)-isocitric acid, is another promising compound. For the first time our process provides large quantities of enantiopure trimethyl (2R,3S)-isocitrate which was used in subsequent chemical transformations to provide new chiral entities for further usage in total synthesis and pharmaceutical research.Oxo- and hydroxy-carboxylic acids are of special interest in organic synthesis. However, their introduction by chemical reactions tends to be troublesome especially with regard to stereoselectivity. We describe herein the biotechnological preparation of selected oxo- and hydroxycarboxylic acids under "green" conditions and their use as promising new building blocks. Thereby, our biotechnological goal was the development of process fundamentals regarding the variable use of renewable raw materials, the development of a multi purpose bioreactor and application of a pilot plant with standard equipment for organic acid production to minimize the technological effort. Furthermore the development of new product isolation procedures, with the aim of direct product recovery, capture of products or single step operation, was necessary. The application of robust and approved microorganisms, also genetically modified, capable of using a wide range of substrates as well as producing a large spectrum of products, was of special importance. Microbiologically produced acids, like 2-oxo-glutaric acid and 2-oxo-D-gluconic acid, are useful educts for the chemical synthesis of hydrophilic triazines, spiro-connected heterocycles, benzotriazines, and pyranoic amino acids. The chiral intermediate of the tricarboxylic acid cycle, (2R,3S)-isocitric acid, is another promising compound. For the first time our process provides large quantities of enantiopure trimethyl (2R,3S)-isocitrate which was used in subsequent chemical transformations to provide new chiral entities for further usage in total synthesis and pharmaceutical research.

AB - Oxo- and hydroxy-carboxylic acids are of special interest in organic synthesis. However, their introduction by chemical reactions tends to be troublesome especially with regard to stereoselectivity. We describe herein the biotechnological preparation of selected oxo- and hydroxycarboxylic acids under "green" conditions and their use as promising new building blocks. Thereby, our biotechnological goal was the development of process fundamentals regarding the variable use of renewable raw materials, the development of a multi purpose bioreactor and application of a pilot plant with standard equipment for organic acid production to minimize the technological effort. Furthermore the development of new product isolation procedures, with the aim of direct product recovery, capture of products or single step operation, was necessary. The application of robust and approved microorganisms, also genetically modified, capable of using a wide range of substrates as well as producing a large spectrum of products, was of special importance. Microbiologically produced acids, like 2-oxo-glutaric acid and 2-oxo-D-gluconic acid, are useful educts for the chemical synthesis of hydrophilic triazines, spiro-connected heterocycles, benzotriazines, and pyranoic amino acids. The chiral intermediate of the tricarboxylic acid cycle, (2R,3S)-isocitric acid, is another promising compound. For the first time our process provides large quantities of enantiopure trimethyl (2R,3S)-isocitrate which was used in subsequent chemical transformations to provide new chiral entities for further usage in total synthesis and pharmaceutical research.Oxo- and hydroxy-carboxylic acids are of special interest in organic synthesis. However, their introduction by chemical reactions tends to be troublesome especially with regard to stereoselectivity. We describe herein the biotechnological preparation of selected oxo- and hydroxycarboxylic acids under "green" conditions and their use as promising new building blocks. Thereby, our biotechnological goal was the development of process fundamentals regarding the variable use of renewable raw materials, the development of a multi purpose bioreactor and application of a pilot plant with standard equipment for organic acid production to minimize the technological effort. Furthermore the development of new product isolation procedures, with the aim of direct product recovery, capture of products or single step operation, was necessary. The application of robust and approved microorganisms, also genetically modified, capable of using a wide range of substrates as well as producing a large spectrum of products, was of special importance. Microbiologically produced acids, like 2-oxo-glutaric acid and 2-oxo-D-gluconic acid, are useful educts for the chemical synthesis of hydrophilic triazines, spiro-connected heterocycles, benzotriazines, and pyranoic amino acids. The chiral intermediate of the tricarboxylic acid cycle, (2R,3S)-isocitric acid, is another promising compound. For the first time our process provides large quantities of enantiopure trimethyl (2R,3S)-isocitrate which was used in subsequent chemical transformations to provide new chiral entities for further usage in total synthesis and pharmaceutical research.

KW - Carboxylic Acids/metabolism

KW - Chemistry Techniques, Synthetic/methods

KW - Gluconates/metabolism

KW - Isocitrates/metabolism

KW - Ketoglutaric Acids/metabolism

KW - Metabolic Engineering/methods

KW - Microbiological Phenomena/genetics

KW - Yarrowia/genetics

U2 - 10.1007/978-94-007-5055-5_19

DO - 10.1007/978-94-007-5055-5_19

M3 - Review article

C2 - 23080261

VL - 64

SP - 391

EP - 423

JO - Subcellular Biochemistry

JF - Subcellular Biochemistry

SN - 0306-0225

ER -

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