Heterologous production of fosfomycin and identification of the minimal biosynthetic gene cluster
Heterologous production of fosfomycin and identification of the minimal biosynthetic gene cluster
复制标题
DOI：
10.1016/j.chembiol.2006.09.007
复制
发表时间：
2006-11-01
影响因子：
--
通讯作者：
Zhao, Huimin
中科院分区：
文献类型：
--
作者：
Woodyer, Ryan D.;Shao, Zengyi;Zhao, Huimin
磷霉素是一种临床上使用的高效抗生素，其对甲氧西林和万古霉素耐药病原体具有活性。在这里，我们报道了一个完整的磷霉素生物合成簇的克隆和鉴定，以及磷霉素在S。青紫色。序列分析结合基因缺失和破坏显示最小簇由fom 1 -4、fomA-D组成。一个LuxR型激活剂，显然是需要异源磷霉素生产也发现类似的13 kb以外的集群，并命名为fomR。基因fomE和fomF，以前被认为是参与磷霉素的生物合成，被证明不是必需的基因破坏。这项工作为磷霉素的生物合成提供了新的见解，并为磷霉素的过量生产和通过生物分子途径工程创造新的类似物打开了大门。
Fosfomycin is a clinically utilized, highly effective antibiotic, which is active against methicillin- and vancomycin-resistant pathogens. Here we report the cloning and characterization of a complete fosfomycin biosynthetic cluster from Streptomyces fradiae and heterologous production of fosfomycin in S. lividans. Sequence analysis coupled with gene deletion and disruption revealed that the minimal cluster consists of fom1-4, fomA-D. A LuxR-type activator that was apparently required for heterologous fosfomycin production was also discovered similar to 13 kb away from the cluster and was named fomR. The genes fomE and fomF, previously thought to be involved in fosfomycin biosynthesis, were shown not to be essential by gene disruption. This work provides new insights into fosfomycin biosynthesis and opens the door for fosfomycin overproduction and creation of new analogs via biomolecular pathway engineering.