Identification and manipulation of the pleuromutilin gene cluster from Clitopilus passeckerianus for increased rapid antibiotic production.
Identification and manipulation of the pleuromutilin gene cluster from Clitopilus passeckerianus for increased rapid antibiotic production.
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DOI：
10.1038/srep25202
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发表时间：
2016-05-04
影响因子：
4.6
通讯作者：
Foster GD
中科院分区：
文献类型：
--
作者：
Bailey AM;Alberti F;Kilaru S;Collins CM;de Mattos-Shipley K;Hartley AJ;Hayes P;Griffin A;Lazarus CM;Cox RJ;Willis CL;O'Dwyer K;Spence DW;Foster GD
来自担子菌Clitopilus passeckerianus的三环二萜抗生素截短侧耳素的半合成衍生物在人类和兽医学中对抗细菌感染是重要的。这些化合物属于唯一一类用于人类应用的新型抗生素，具有新颖的作用模式和缺乏交叉耐药性，代表了具有巨大潜力的一类。担子菌类真菌是双孢菌，一般不适合菌株改良。我们报告了七基因截短侧耳素基因簇的鉴定，并验证了使用各种靶向方法旨在增加C. Passeckerianus，没有实现产量的提高。在Aspergillusplasma中重建了截短侧耳素的7个基因簇，从而在子囊菌中产生截短侧耳素，产量显著增加（2106%）。这是第一个在子囊菌中成功表达的来自担子菌的基因簇，为开发代谢丰富但传统上被忽视的真菌群铺平了道路。
Semi-synthetic derivatives of the tricyclic diterpene antibiotic pleuromutilin from the basidiomycete Clitopilus passeckerianus are important in combatting bacterial infections in human and veterinary medicine. These compounds belong to the only new class of antibiotics for human applications, with novel mode of action and lack of cross-resistance, representing a class with great potential. Basidiomycete fungi, being dikaryotic, are not generally amenable to strain improvement. We report identification of the seven-gene pleuromutilin gene cluster and verify that using various targeted approaches aimed at increasing antibiotic production in C. passeckerianus, no improvement in yield was achieved. The seven-gene pleuromutilin cluster was reconstructed within Aspergillus oryzae giving production of pleuromutilin in an ascomycete, with a significant increase (2106%) in production. This is the first gene cluster from a basidiomycete to be successfully expressed in an ascomycete, and paves the way for the exploitation of a metabolically rich but traditionally overlooked group of fungi.