Development of reaction systems for ATP regeneration from the inexpensive bulk chemical ethylene glycol

开发从廉价的大宗化学品乙二醇再生 ATP 的反应系统

• 批准号: 450319558
• 负责人: Professor Dr. Andreas Liese
• 金额: --
• 依托单位: Institut für Naturstofftechnik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/450319558?language=en
• 关键词: Development; reaction; systems; ATP; regeneration

In this project, enzyme systems for the cost-effective regeneration of ATP in technical reaction systems will be developed. The project is planned as a joint project of the working groups of Prof. Thomas Walther (Professorship of Bioprocess Engineering, TU Dresden) and of Prof. Andreas Liese (Chair of Technical Biocatalysis, TU Hamburg), where AG Walther is responsible for the design and construction of the ATP regenerating enzyme cascades as well as for the optimization of individual enzyme activities, and the AG Liese will work on the reaction engineering and optimization of the reaction systems as well as transfer to larger scales.ATP regenerating reaction systems have a variety of industrial applications. Examples include the synthesis of phosphorylated fine chemicals, syntheses with phosphorylation as an intermediate step and cell-free protein expression. A major obstacle to the commercialization of ATP-dependent, cell-free, product syntheses is the sometimes very high price of the substrates and cofactors used for ATP regeneration.To solve this technical problem, the development of reaction systems is proposed, which allow an ATP regeneration of the low-cost and potentially "green" bulk chemical ethylene glycol. The implementation of the designed enzyme cascades requires the enhancement of enzyme activity on a non-natural substrate. This increase in activity is to be achieved through a combination of rational and evolutionary protein design. In addition, a reaction-technical analysis and optimization of the transfer of the various systems on a technical scale is examined.The enzyme cascades for the regeneration of ATP will be constructed from isolated enzymes as well as be implemented in whole-cell biocatalysts. In each case, the ATP-regenerating systems are coupled to the synthesis of an ATP-consuming reaction for the synthesis of a phosphorylated or non-phosphorylated end product in order to determine advantages and limits of both design variants.The reaction cascades described have the potential to be developed into a new universal ATP regeneration system, which can also be used on an industrial scale.

在该项目中，将开发用于技术反应系统中ATP的成本效益再生的酶系统。该项目计划作为托马斯瓦尔特教授工作组的联合项目（生物工艺工程教授，德累斯顿工业大学）和Andreas Liese教授（技术生物催化主席，汉堡工业大学），其中AG Walther负责ATP再生酶级联的设计和构建以及单个酶活性的优化，AG Liese将致力于反应工程和反应系统的优化以及向更大规模的转移。ATP再生反应系统具有多种工业应用。例子包括磷酸化精细化学品的合成，以磷酸化为中间步骤的合成和无细胞蛋白质表达。ATP依赖的、无细胞的产物合成的商业化的主要障碍是用于ATP再生的底物和辅因子的有时非常高的价格。为了解决这个技术问题，提出了反应系统的开发，其允许低成本和潜在的“绿色”散装化学品乙二醇的ATP再生。所设计的酶级联的实施需要在非天然底物上增强酶活性。这种活性的增加是通过合理和进化蛋白质设计的组合来实现的。此外，一个反应技术分析和优化的各种系统的技术规模的转移检查。酶级联再生ATP将构建从分离的酶，以及在全细胞生物催化剂中实施。在每种情况下，ATP再生系统耦合到合成的ATP消耗反应的磷酸化或非磷酸化的最终产物的合成，以确定两种设计variants.The反应级联描述的优点和限制有可能被开发成一个新的通用ATP再生系统，这也可以在工业规模上使用。