Application of an aculeacin A acylase from Actinoplanes utahensis SW1311 in syntheses of echinocandins
Application of an aculeacin A acylase from Actinoplanes utahensis SW1311 in syntheses of echinocandins
复制标题
犹他游动放线菌SW1311阿库莱辛A酰化酶在棘白菌素合成中的应用
DOI：
10.3785/j.issn.1008-9209.2016.12.061
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发表时间：
2017-03
期刊：
影响因子：
--
通讯作者：
江辉
中科院分区：
文献类型：
--
作者：
冯国栋;许永锋;陈建烽;赵万忠;王欣;张小晟;江辉
棘白菌素是第一类靶向真菌细胞壁的抗真菌药物。米卡芬净和阿尼芬净两种抗真菌药物已广泛应用于临床。它们的合成包括一个基本过程：从FR 901379和棘白菌素B（ECB）水解除去脂肪酰基侧链，生成环状六肽核。本研究分离到一株对FR 901379和青霉素Ⅴ均具有酰化酶活性的犹他游动放线菌SW 1311。然后，从天蓝色链霉菌A3（2）中克隆到了含有棘球蛋白A酰化酶（AAC）基因的重组菌株。utahensis SW 1311的构建。结果表明，该重组菌的AAC活性是A. utahensis SW 1311.重组菌发酵时间比A.
utahensis SW 1311.本研究结果不仅为AAC在米卡芬净合成中的应用提供了新的思路，而且为AAC基因寻找了一种新的合适宿主。
Echinocandins are the first class of antifungals to target fungal cell wall. Two antifungals, including micafungin and anidulafungin, have been widely used in clinic. The synthesis of them includes an essential process: hydrolytic removal of fatty acyl side chains from FR901379 and echinocandin B (ECB) to generate cyclic hexapeptide nuclei. In this study, Actinoplanes utahensis SW1311 with acylase activity was isolated for both FR901379 and penicillin Ⅴ. Then a recombinant Streptomyces coelicolor A3(2) harboring aculeacin A acylase (AAC) gene from A. utahensis SW1311 was constructed. The result showed that the AAC activity produced by the recombinant strain was 4.6-fold higher than that of A. utahensis SW1311. Additionally, the fermentation time of the recombinant strain was 30% shorter than that of A.
utahensis SW1311. The results not only provide a new application of AAC for micafungin synthesis but also identify a new suitable host for AAC gene.