Chapter

Reprogramming Microbial Metabolic Pathways

Volume 64 of the series Subcellular Biochemistry pp 391-423

Date:

Microbiologically Produced Carboxylic Acids Used as Building Blocks in Organic Synthesis

  • Andreas AurichAffiliated withHelmholtz-Centre for Environmental Research – UFZ
  • , Robert SpechtAffiliated withHelmholtz-Centre for Environmental Research – UFZ
  • , Roland A. MüllerAffiliated withHelmholtz-Centre for Environmental Research – UFZ
  • , Ulrich StottmeisterAffiliated withHelmholtz-Centre for Environmental Research – UFZ Email author 
  • , Venelina YovkovaAffiliated withInstitute of Microbiology, Dresden University of Technology
  • , Christina OttoAffiliated withInstitute of Microbiology, Dresden University of Technology
  • , Martina HolzAffiliated withInstitute of Microbiology, Dresden University of Technology
  • , Gerold BarthAffiliated withInstitute of Microbiology, Dresden University of Technology
  • , Philipp HeretschAffiliated withInstitute of Organic Chemistry, University of Leipzig
    • , Franziska A. ThomasAffiliated withInstitute of Organic Chemistry, University of Leipzig
    • , Dieter SickerAffiliated withInstitute of Organic Chemistry, University of Leipzig
    • , Athanassios GiannisAffiliated withInstitute of Organic Chemistry, University of Leipzig

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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

Biotechnical cultivation Gluconobacter oxydans (2R,3S)-Isocitric acid Microorganism 2-Oxo-d-gluconic acid 2-Oxoglutaric acid Strain improvement Yarrowia lipolytica