酰基酶在棘白霉素类抗真菌药物生产中的应用（英文）
发布时间：2018-11-01 18:51
【摘要】：棘白霉素类化合物是最早发现的能抑制真菌细胞壁合成的天然产物,其中阿尼芬净和米卡芬净2种棘白霉素衍生物已经被广泛地应用于临床。它们的合成途径包括一个关键步骤,将天然产物棘白霉素B(ECB)和FR901379的6元环状多肽核上的长链脂肪酰侧链分别用非天然酰基侧链取代。阿库来菌素A酰基酶(AAC)和FR901379酰基酶能催化ECB和FR901379脂肪酰侧链的水解,生成的ECB和FR901379的环状多肽核可用于阿尼芬净和米卡芬净的生产。AAC和FR901379酰基酶对棘白霉素类化合物的酰基有很强的水解活性,而且这2个酶能在链霉菌中异源生产,因此它们成为棘白霉素类药物工业生产中广泛应用的绿色生物催化剂。本文介绍了ACC和FR901379酰基酶的酶学特性与应用。
[Abstract]:Echinomycin compounds are the first natural products which can inhibit the cell wall synthesis of fungi. Among them, two kinds of Acanthophanetin derivatives have been widely used in clinic. Their synthesis involves a key step in replacing the long chain aliphatic side chains on the six-member cyclic polypeptide nuclei of the natural products B (ECB) and FR901379 with non-natural acyl side chains, respectively. Acylase (AAC) and FR901379 acylase can catalyze the hydrolysis of aliphatic side chains of ECB and FR901379. The cyclic polypeptide nuclei of ECB and FR901379 can be used in the production of arnifen and mikafennet. AAC and FR901379 acylase have strong hydrolysis activity for acyl groups of spinomycin compounds, and these two enzymes can be produced in Streptomyces heterogenous. Therefore, they have been widely used as green biocatalysts in the industrial production of acanthomycin. The enzymatic properties and applications of ACC and FR901379 acylase were introduced in this paper.
【作者单位】： 华东医药集团新药研究院有限公司;浙江大学生命科学学院;
【基金】：国家自然科学基金(No.31670008) 浙江省自然科学基金(No.LR16H300001)
【分类号】：R915
本文编号：2304795
[Abstract]:Echinomycin compounds are the first natural products which can inhibit the cell wall synthesis of fungi. Among them, two kinds of Acanthophanetin derivatives have been widely used in clinic. Their synthesis involves a key step in replacing the long chain aliphatic side chains on the six-member cyclic polypeptide nuclei of the natural products B (ECB) and FR901379 with non-natural acyl side chains, respectively. Acylase (AAC) and FR901379 acylase can catalyze the hydrolysis of aliphatic side chains of ECB and FR901379. The cyclic polypeptide nuclei of ECB and FR901379 can be used in the production of arnifen and mikafennet. AAC and FR901379 acylase have strong hydrolysis activity for acyl groups of spinomycin compounds, and these two enzymes can be produced in Streptomyces heterogenous. Therefore, they have been widely used as green biocatalysts in the industrial production of acanthomycin. The enzymatic properties and applications of ACC and FR901379 acylase were introduced in this paper.
【作者单位】： 华东医药集团新药研究院有限公司;浙江大学生命科学学院;
【基金】：国家自然科学基金(No.31670008) 浙江省自然科学基金(No.LR16H300001)
【分类号】：R915
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