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Systems Biocatalysis: Development and engineering of cell-free 'artificial metabolisms'' for preparative multi-enzymatic synthesis

机译:系统生物催化:用于制备多酶合成的无细胞“人工代谢”的开发和工程设计

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摘要

Systems Biocatalysis is an emerging concept of organizing enzymes in vitro to construct complex reaction cascades for an efficient, sustainable synthesis of valuable chemical products. The strategy merges the synthetic focus of chemistry with the modular design of biological systems, which is similar to metabolic engineering of cellular production systems but can be realized at a far lower level of complexity from a true reductionist approach. Such operations are free from material erosion by competing metabolic pathways, from kinetic restrictions by physical barriers and regulating circuits, and from toxicity problems with reactive foreign substrates, which are notorious problems in whole-cell systems. A particular advantage of cell-free concepts arises from the inherent opportunity to construct novel biocatalytic reaction systems for the efficient synthesis of non-natural products ("artificial metabolisms'') by using enzymes specifically chosen or engineered for non-natural substrate promiscuity. Examples illustrating the technology from our laboratory are discussed.
机译:系统生物催化是一种新兴的概念,它在体外组织酶以构建复杂的反应级联,从而有效,可持续地合成有价值的化学产品。该策略将化学的综合重点与生物系统的模块化设计相结合,这与细胞生产系统的代谢工程相似,但是通过真正的还原论方法可以实现更低的复杂性。这样的操作不受竞争性代谢途径的物质侵蚀,物理屏障和调节回路的动力学限制以及反应性异物底物的毒性问题,而这些问题在全细胞系统中是众所周知的问题。无细胞概念的一个特殊优势来自固有的机会,即通过使用专门为非天然底物混杂而选择或设计的酶来构建新颖的生物催化反应系统,以有效合成非天然产物(“人工代谢”)。讨论了说明我们实验室技术的方法。

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