Engineered production of iso-migrastatin in heterologous Streptomyces hosts
Engineered production of iso-migrastatin in heterologous Streptomyces hosts
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DOI：
10.1016/j.bmc.2008.10.074
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发表时间：
2009-03-15
影响因子：
3.5
通讯作者：
Shen, Ben
中科院分区：
文献类型：
--
作者：
Feng, Zhiyang;Wang, Liyan;Shen, Ben
含有戊二酰亚胺的聚酮，如米非司他丁(MGS)，以其抑制肿瘤细胞迁移的能力而闻名。我们以前已经证明，MGS是由异米非司他丁(iso-MGS)通过水介导的扩环重排而来的。构建了异亚甲基葡萄糖产生菌钝顶链霉菌NRRL18993的细菌人工染色体文库。从该文库中鉴定出含有完整的iso-MGS生物合成基因簇的BAC克隆pBS11001。将pBS11001动员到5株异源链霉菌中，获得了重组菌株SB11001、SB11002、SB11003、SB11004和SB11005。在一套标准的培养基和发酵条件下，重组菌株都产生了相同的PRO。LE与钝顶螺旋藻NRRL18993相同。这些发现突出了基于BAC的技术在异种链霉菌模型宿主中用于天然产品生产和工程的强度和灵活性。(C)2008爱思唯尔有限公司。保留所有权利。
Glutarimide-containing polyketides such as migrastatin (MGS) are well known for their ability to inhibit tumor cell migration. We have previously shown that MGS is derived from iso-migrastatin (iso-MGS) via a H2O-mediated ring-expansion rearrangement. A bacterial artificial chromosome (BAC) library of Streptomyces platensis NRRL18993, an iso-MGS producer, was constructed. From this library, pBS11001, a BAC clone harboring the intact iso-MGS biosynthetic gene cluster, was identified. Mobilization of pBS11001 into five heterologous Streptomyces hosts afforded recombinant strains, SB11001, SB11002, SB11003, SB11004, and SB11005, respectively. Under a standard set of media and fermentation conditions, the recombinant strains all produced the same pro. le of iso-MGS as that of S. platensis NRRL18993. These findings highlight the strength and flexibility of the BAC-based technology for natural product production and engineering in heterologous Streptomyces model hosts. (C) 2008 Elsevier Ltd. All rights reserved.