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手性胺合成的酶促途径:蛋白质工程与工艺优化

Enzymatic Routes for Chiral Amine Synthesis: Protein Engineering and Process Optimization.

作者信息

Vikhrankar Sayali Shantaram, Satbhai Seema, Kulkarni Priyanka, Ranbhor Ranjit, Ramakrishnan Vibin, Kodgire Prashant

机构信息

Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, MP, India.

Sevit Healthcare Private Limited, Pune, MH, India.

出版信息

Biologics. 2024 Jun 25;18:165-179. doi: 10.2147/BTT.S446712. eCollection 2024.

DOI:10.2147/BTT.S446712
PMID:38948006
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11214570/
Abstract

Chiral amines are essential motifs in pharmaceuticals, agrochemicals, and specialty chemicals. While traditional chemical routes to chiral amines often lack stereoselectivity and require harsh conditions, biocatalytic methods using engineered enzymes can offer high efficiency and selectivity under sustainable conditions. This review discusses recent advances in protein engineering of transaminases, oxidases, and other enzymes to improve catalytic performance. Strategies such as directed evolution, immobilization, and computational redesign have expanded substrate scope and enhanced efficiency. Furthermore, process optimization guided by techno-economic assessments has been crucial for establishing viable biomanufacturing routes. Combining state-of-the-art enzyme engineering with multifaceted process development will enable scalable, economical enzymatic synthesis of diverse chiral amine targets.

摘要

手性胺是药物、农用化学品和特种化学品中的重要结构单元。虽然传统的手性胺化学合成路线往往缺乏立体选择性且需要苛刻的条件,但使用工程酶的生物催化方法可以在可持续的条件下提供高效率和选择性。本文综述了转氨酶、氧化酶和其他酶的蛋白质工程方面的最新进展,以提高催化性能。定向进化、固定化和计算重新设计等策略扩大了底物范围并提高了效率。此外,以技术经济评估为指导的工艺优化对于建立可行的生物制造路线至关重要。将先进的酶工程与多方面的工艺开发相结合,将实现各种手性胺目标的可扩展、经济的酶促合成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4b6/11214570/a48926085748/BTT-18-165-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4b6/11214570/d2636a6bf1b1/BTT-18-165-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4b6/11214570/669a0b44f8ac/BTT-18-165-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4b6/11214570/b780c520c70f/BTT-18-165-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4b6/11214570/231fbf435972/BTT-18-165-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4b6/11214570/a48926085748/BTT-18-165-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4b6/11214570/d2636a6bf1b1/BTT-18-165-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4b6/11214570/669a0b44f8ac/BTT-18-165-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4b6/11214570/b780c520c70f/BTT-18-165-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4b6/11214570/231fbf435972/BTT-18-165-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4b6/11214570/a48926085748/BTT-18-165-g0005.jpg

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