Deoxysugar pathway interchange for erythromycin analogues heterologously produced through Escherichia coli
Deoxysugar pathway interchange for erythromycin analogues heterologously produced through Escherichia coli
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DOI：
10.1016/j.ymben.2013.09.005
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发表时间：
2013-11-01
影响因子：
8.4
通讯作者：
Pfeifer, Blaine A.
中科院分区：
文献类型：
--
作者：
Jiang, Ming;Zhang, Haoran;Pfeifer, Blaine A.
红霉素的整个生物合成途径可以细分为大环聚酮的形成和聚酮的剪裁，以产生最终的生物活性分子。在这项研究中，天然脱氧糖剪裁反应被交换，目的是为了展示替代最终红霉素化合物的生产。将D-脱糖胺和L-麦芽糖脱氧糖途径替换为D-麦芽糖和D-橄榄糖途径，通过大肠杆菌异源系统产生新的红霉素类似物。两个类似物对多种耐药枯草芽孢杆菌菌株均显示出生物活性。除了展示了生物合成系统适应其他剪裁途径的内在灵活性外，这些结果还为利用大肠杆菌平台生产红霉素类似物提供了初步尝试。(C)2013 Elsevier Inc.保留所有权利。
The overall erythromycin biosynthetic pathway can be sub-divided into macrocyclic polyketide formation and polyketide tailoring to produce the final bioactive molecule. In this study, the native deoxysugar tailoring reactions were exchanged for the purpose of demonstrating the production of alternative final erythromycin compounds. Both the D-desosamine and L-mycarose deoxysugar pathways were replaced with the alternative D-mycaminose and D-olivose pathways to produce new erythromycin analogues through the Escherichia coli heterologous system. Both analogues exhibited bioactivity against multiple antibiotic-resistant Bacillus subtilis strains. Besides demonstrating an intrinsic flexibility for the biosynthetic system to accommodate alternative tailoring pathways, the results offer an initial attempt to leverage the E. coli platform for erythromycin analogue production. (C) 2013 Elsevier Inc. All rights reserved.