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首页> 外文期刊>The Journal of Antibiotics: An International Journal >Analysis of Modular-iterative Mixed Biosynthesis of Lankacidin by Heterologous Expression and Gene Fusion.
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Analysis of Modular-iterative Mixed Biosynthesis of Lankacidin by Heterologous Expression and Gene Fusion.

机译:异源表达和基因融合分析Lancancidin的模块-迭代混合生物合成。

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摘要

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.
机译:Lankacidin是一种独特的17元大环抗生素,与通常的偶数大环内酯类药物不同。基于罗氏链霉菌线性质粒pSLA2-L上编码的lankacidin生物合成簇的基因组织,我们先前提出了关于lankacidin的模块迭代混合聚酮化合物生物合成的假说。本文的两个实验证据进一步加强了这一假设。兰卡丁素簇(lkcA-lkcO)在淡青链霉菌中的异源表达导致产生兰卡酸丁酚A,表明该基因簇足以合成兰卡酸丁骨架。此外,lkcF和lkcG的基因融合剂产生的兰卡酸与亲代菌株的水平相似,这表明LkcF蛋白的迭代功能不太可能。这些结果与以下假设一致:LkcC被使用了四次,LkcA,LkcF和LkcG被模块化地使用以完成八个缩合反应,从而产生兰卡地宁骨架。

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