Feng Zhiyang, Wang Liyan, Rajski Scott R, Xu Zhinan, Coeffet-LeGal Marie F, Shen Ben
Division of Pharmaceutical Sciences, University of Wisconsin-Madison, Madison, WI 53705, USA.
Bioorg Med Chem. 2009 Mar 15;17(6):2147-53. doi: 10.1016/j.bmc.2008.10.074. Epub 2008 Nov 5.
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 H(2)O-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 profile 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.
含戊二酰亚胺的聚酮化合物，如米格拉他汀（MGS），以其抑制肿瘤细胞迁移的能力而闻名。我们之前已经表明，MGS是通过水介导的扩环重排从异米格拉他汀（iso-MGS）衍生而来的。构建了产异米格拉他汀的天蓝色链霉菌NRRL18993的细菌人工染色体（BAC）文库。从该文库中，鉴定出了携带完整异米格拉他汀生物合成基因簇的BAC克隆pBS11001。将pBS11001分别导入五个异源链霉菌宿主中，得到了重组菌株SB11001、SB11002、SB11003、SB11004和SB11005。在一组标准的培养基和发酵条件下，这些重组菌株产生的异米格拉他汀谱与天蓝色链霉菌NRRL18993相同。这些发现突出了基于BAC的技术在异源链霉菌模型宿主中进行天然产物生产和工程改造的优势和灵活性。
