Analysis of Modular-iterative Mixed Biosynthesis of Lankacidin by Heterologous Expression and Gene Fusion
Analysis of Modular-iterative Mixed Biosynthesis of Lankacidin by Heterologous Expression and Gene Fusion
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DOI：
10.1038/ja.2007.90
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发表时间：
2007-11
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影响因子：
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通讯作者：
S. Tatsuno;K. Arakawa;H. Kinashi
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文献类型：
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作者：
S. Tatsuno;K. Arakawa;H. Kinashi
Lankacidin是一种独特的17元大环抗生素，不同于通常的偶数元大环内酯。基于链霉菌线性质粒pSLA 2-L上编码的兰卡菌素生物合成簇的基因组织，我们以前提出了一个假设，模块迭代混合聚酮生物合成兰卡菌素。本文的两个实验证据进一步加强了这一假设。在变铅青链霉菌中异源表达lankacidin簇（lkcA-lkcO）导致lankacidinol A的产生，表明该基因簇足以合成lankacidin骨架。此外，lkcF和lkcG的基因融合体以与亲本菌株相似的水平产生lankacidin，这表明LkcF蛋白的迭代功能是不可能的。这些结果与LkcC被使用四次并且LkcA、LkcF和LkcG被模块化地使用以完成导致lankacidin骨架的八个缩合反应的假设一致。
Lankacidin is a unique 17-membered macrocyclic antibiotic different from usual even-membered macrolides. Based on the gene organization of the lankacidin biosynthetic cluster coded on the linear plasmid pSLA2-L in Streptomyces rochei, we previously proposed a hypothesis of modular-iterative mixed polyketide biosynthesis for lankacidin. Two experimental evidences in this paper further strengthened this hypothesis. Heterologous expression of the lankacidin cluster (lkcA-lkcO) in Streptomyces lividans resulted in lankacidinol A production, indicating that the gene cluster is sufficient for the synthesis of the lankacidin skeleton. In addition, a gene fusant of lkcF and lkcG produced lankacidin at a similar level to the parent strain, suggesting that an iterative function of the LkcF protein is unlikely. These results are consistent with the hypothesis that LkcC is used four times and LkcA, LkcF and LkcG are used modularly to accomplish eight condensation reactions leading to the lankacidin skeleton.