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工业相关酶级联反应在药物合成中的应用及其生态评估。

Industrially Relevant Enzyme Cascades for Drug Synthesis and Their Ecological Assessment.

机构信息

Chair for Bioprocess Engineering, Department of Biochemical and Chemical Engineering, TU Dortmund University, D-44227 Dortmund, Germany.

出版信息

Int J Mol Sci. 2022 Mar 25;23(7):3605. doi: 10.3390/ijms23073605.

DOI:10.3390/ijms23073605
PMID:35408960
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8998672/
Abstract

Environmentally friendly and sustainable processes for the production of active pharmaceutical ingredients (APIs) gain increasing attention. Biocatalytic synthesis routes with enzyme cascades support many stated green production principles, for example, the reduced need for solvents or the biodegradability of enzymes. Multi-enzyme reactions have even more advantages such as the shift of the equilibrium towards the product side, no intermediate isolation, and the synthesis of complex molecules in one reaction pot. Despite the intriguing benefits, only a few enzyme cascades have been applied in the pharmaceutical industry so far. However, several new enzyme cascades are currently being developed in research that could be of great importance to the pharmaceutical industry. Here, we present multi-enzymatic reactions for API synthesis that are close to an industrial application. Their performances are comparable or exceed their chemical counterparts. A few enzyme cascades that are still in development are also introduced in this review. Economic and ecological considerations are made for some example cascades to assess their environmental friendliness and applicability.

摘要

环保且可持续的原料药(API)生产工艺日益受到关注。酶级联的生物催化合成路线支持许多既定的绿色生产原则,例如减少对溶剂的需求或酶的生物降解性。多酶反应甚至具有更多优势,例如向产物侧移动平衡、无需中间分离以及在一个反应釜中合成复杂分子。尽管具有诱人的优势,但迄今为止,此类酶级联在制药行业中仅得到了有限的应用。然而,目前研究中正在开发几种新的酶级联,这对制药行业可能具有重要意义。在这里,我们展示了接近工业化应用的 API 合成的多酶反应。它们的性能可与化学对照物相媲美或超过化学对照物。本文还介绍了一些仍在开发中的酶级联。针对一些示例级联进行了经济和生态方面的考虑,以评估它们的环境友好性和适用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b29/8998672/72ae9b396c23/ijms-23-03605-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b29/8998672/2a85ccfb22b0/ijms-23-03605-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b29/8998672/72ae9b396c23/ijms-23-03605-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b29/8998672/2a85ccfb22b0/ijms-23-03605-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b29/8998672/72ae9b396c23/ijms-23-03605-g002.jpg

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