Design of an electrochemical bioproduction system for piperazines

该跨学科研究项目涉及2240优先计划的两个基本领域，即用于增值产品电生物合成的微生物代谢工程以及用于高效生物电化学过程的电极和反应器工程。固定二氧化碳和氧化h2的Knallgas微生物富营养化Ralstonia eutropha是一种多功能平台生物，可以生产各种化学物质和生物聚合物。含氮杂环化合物，如哌嗪，是在广泛的药用和生物活性天然产品中发现的非常有价值的组成部分。缺乏直接合成C-和n -取代哌嗪的有效方法是释放这些系统的全部治疗潜力的主要障碍之一。nadph依赖的亚胺还原酶催化二羰基与二胺的还原偶联，生成相应的哌嗪产物。这个反应需要两个等价的昂贵的NADPH辅助因子，它需要不断地回收用于实际的大规模应用。在这个项目中，我们的目标是设计一个可堆叠的类似pem的反应器，将富营养菌的二氧化碳固定代谢与电驱动的还原物供应连接起来，用于连续流动合成哌嗪。

This interdisciplinary research project addresses two fundamental areas of the Priority Program 2240, namely the metabolic engineering of microorganism for electro-biosynthesis of value-added products as well as electrode and reactor engineering for efficient bio-electrochemical processes. The CO2-fixing and H2-oxidising Knallgas microorganism Ralstonia eutropha represents a versatile platform organism to produce various chemicals and biopolymers. Nitrogen-containing heterocycles such as piperazines are highly valuable building blocks found in a wide range of medicinal and bioactive natural products. The lack of efficient methods to directly synthesize C- and N-substituted piperazines represents one of the major hurdles in unleashing the full therapeutic potential of these systems. The NADPH-dependent imine reductases catalyze the reductive coupling of dicarbonyls with diamines to generate the corresponding piperazine products. This reaction requires two equivalents of the costly NADPH cofactor, which needs to be continuously recycled for practical large-scale applications. In this project, we aim to engineer a stackable PEM-like reactor that links the CO2 fixation metabolism of R. eutropha with electrodriven supply of reducing equivalents for the continuous flow synthesis of piperazines.