Aurich Andreas, Specht Robert, Müller Roland A, Stottmeister Ulrich, Yovkova Venelina, Otto Christina, Holz Martina, Barth Gerold, Heretsch Philipp, Thomas Franziska A, Sicker Dieter, Giannis Athanassios
Helmholtz-Centre for Environmental Research - UFZ, Permoserstr. 15, 04318, Leipzig, Germany.
Subcell Biochem. 2012;64:391-423. doi: 10.1007/978-94-007-5055-5_19.
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.
氧代羧酸和羟基羧酸在有机合成中具有特殊意义。然而，通过化学反应引入它们往往比较麻烦，尤其是在立体选择性方面。本文中，我们描述了在“绿色”条件下生物技术制备特定氧代羧酸和羟基羧酸的方法，以及它们作为有前景的新型结构单元的用途。因此，我们的生物技术目标是开发关于可再生原料可变使用的工艺基础，开发多功能生物反应器，并应用配备有机酸生产标准设备的中试工厂，以尽量减少技术工作量。此外，开发旨在直接产品回收、产物捕获或单步操作的新产品分离程序也是必要的。应用稳健且经过批准的微生物，包括经过基因改造的、能够利用多种底物并生产多种产物的微生物，具有特别重要的意义。微生物生产的酸，如2-氧代戊二酸和2-氧代-D-葡萄糖酸，是用于亲水性三嗪、螺环连接杂环、苯并三嗪和吡喃氨基酸化学合成的有用原料。三羧酸循环的手性中间体(2R,3S)-异柠檬酸是另一种有前景的化合物。我们的工艺首次提供了大量对映体纯的三甲基(2R,3S)-异柠檬酸盐，其用于后续的化学转化，以提供新的手性实体，供全合成和药物研究进一步使用。氧代羧酸和羟基羧酸在有机合成中具有特殊意义。然而，通过化学反应引入它们往往比较麻烦，尤其是在立体选择性方面。本文中，我们描述了在“绿色”条件下生物技术制备特定氧代羧酸和羟基羧酸的方法，以及它们作为有前景的新型结构单元的用途。因此，我们的生物技术目标是开发关于可再生原料可变使用的工艺基础，开发多功能生物反应器，并应用配备有机酸生产标准设备的中试工厂，以尽量减少技术工作量。此外，开发旨在直接产品回收、产物捕获或单步操作的新产品分离程序也是必要的。应用稳健且经过批准的微生物，包括经过基因改造的、能够利用多种底物并生产多种产物的微生物，具有特别重要的意义。微生物生产的酸，如2-氧代戊二酸和2-氧代-D-葡萄糖酸，是用于亲水性三嗪、螺环连接杂环、苯并三嗪和吡喃氨基酸化学合成的有用原料。三羧酸循环的手性中间体(2R,3S)-异柠檬酸是另一种有前景的化合物。我们的工艺首次提供了大量对映体纯的三甲基(2R,3S)-异柠檬酸盐，其用于后续的化学转化，以提供新的手性实体，供全合成和药物研究进一步使用。
