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微生物脂肪酶及其在药物砌块生产中的潜力。

Microbial Lipases and Their Potential in the Production of Pharmaceutical Building Blocks.

机构信息

Laboratorio de Investigación en Biocatálisis y Biotransformaciones (LIBB), Grupo de Investigación en Ingeniería de los Procesos Agroalimentarios y Biotecnológicos (GIPAB), Departamento de Química, Universidad del Valle, Cali 76001, Colombia.

Grupo de Investigación de Materiales Porosos (GIMPOAT), Departamento de Química, Universidad del Tolima, Ibague 730001, Colombia.

出版信息

Int J Mol Sci. 2022 Sep 1;23(17):9933. doi: 10.3390/ijms23179933.

DOI:10.3390/ijms23179933
PMID:36077332
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9456414/
Abstract

Processes involving lipases in obtaining active pharmaceutical ingredients (APIs) are crucial to increase the sustainability of the industry. Despite their lower production cost, microbial lipases are striking for their versatile catalyzing reactions beyond their physiological role. In the context of taking advantage of microbial lipases in reactions for the synthesis of API building blocks, this review focuses on: (i) the structural origins of the catalytic properties of microbial lipases, including the results of techniques such as single particle monitoring (SPT) and the description of its selectivity beyond the Kazlauskas rule as the "Mirror-Image Packing" or the "Key Region(s) rule influencing enantioselectivity" (KRIE); (ii) immobilization methods given the conferred operative advantages in industrial applications and their modulating capacity of lipase properties; and (iii) a comprehensive description of microbial lipases use as a conventional or promiscuous catalyst in key reactions in the organic synthesis (Knoevenagel condensation, Morita-Baylis-Hillman (MBH) reactions, Markovnikov additions, Baeyer-Villiger oxidation, racemization, among others). Finally, this review will also focus on a research perspective necessary to increase microbial lipases application development towards a greener industry.

摘要

在获得活性药物成分 (API) 的过程中,涉及脂肪酶的过程对提高行业的可持续性至关重要。尽管微生物脂肪酶的生产成本较低,但它们在超越生理作用的多功能催化反应方面引人注目。在利用微生物脂肪酶进行 API 构建块合成反应的背景下,本文重点介绍了:(i)微生物脂肪酶催化特性的结构起源,包括单颗粒监测 (SPT) 等技术的结果,以及超越 Kazlauskas 规则的选择性描述,即“镜像包装”或“影响对映选择性的关键区域 (KRIE)规则”;(ii)固定化方法,鉴于其在工业应用中具有操作性优势,以及对脂肪酶特性的调节能力;以及(iii)微生物脂肪酶作为常规或混杂催化剂在有机合成中关键反应(Knoevenagel 缩合、Morita-Baylis-Hillman (MBH) 反应、Markovnikov 加成、Baeyer-Villiger 氧化、外消旋化等)中的综合应用描述。最后,本文还将重点介绍增加微生物脂肪酶应用开发以实现更绿色工业所需的研究展望。

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