当前位置：
X-MOL 学术
›
J. Nat. Prod.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Reconstitution of Kinamycin Biosynthesis within the Heterologous Host Streptomyces albus J1074
Journal of Natural Products ( IF 3.3 ) Pub Date : 2018-01-17 00:00:00 , DOI: 10.1021/acs.jnatprod.7b00652 Xiangyang Liu 1 , Dongxu Liu 1 , Min Xu 1 , Meifeng Tao 1 , Linquan Bai 1 , Zixin Deng 1 , Blaine A. Pfeifer 2 , Ming Jiang 1
Journal of Natural Products ( IF 3.3 ) Pub Date : 2018-01-17 00:00:00 , DOI: 10.1021/acs.jnatprod.7b00652 Xiangyang Liu 1 , Dongxu Liu 1 , Min Xu 1 , Meifeng Tao 1 , Linquan Bai 1 , Zixin Deng 1 , Blaine A. Pfeifer 2 , Ming Jiang 1
Affiliation
|
Diazofluorene compounds such as kinamycin and lomaiviticin feature unique molecular structures and compelling medicinal bioactivities. However, a complete understanding of the biosynthetic details for this family of natural products has yet to be fully elucidated. In addition, a lack of genetically and technically amenable production hosts has limited access to the full medicinal potential of these compounds. Here, we report the capture of the complete kinamycin gene cluster from Streptomyces galtieri Sgt26 by bacterial artificial chromosome cloning, confirmed by successful production of kinamycin in the heterologous host Streptomyces albus J1074. Sequence analysis and a series of gene deletion experiments revealed the boundary of the cluster, which spans 75 kb DNA. To probe the last step in biosynthesis, acetylation of kinamcyin F to kinamycin D, gene knockout, and complementation experiments identified a single gene product involved with final acetylation conversions. This study provides full genetic information for the kinamycin gene cluster from S. galtieri Sgt26 and establishes heterologous biosynthesis as a production platform for continued mechanistic assessment of compound formation and utilization.
中文翻译：
异源寄主链霉菌J1074内卡那霉素生物合成的重建
重氮芴化合物（如卡那霉素和洛麦维汀）具有独特的分子结构和引人注目的药用生物活性。然而，尚未完全阐明对该天然产物家族的生物合成细节的完全理解。另外，缺乏遗传和技术上适合的生产宿主限制了这些化合物的全部药用潜力。在这里，我们报告了通过细菌人工染色体克隆捕获了来自金链霉菌Sgt26的完整的金那霉素基因簇，并通过在异源宿主链霉菌中成功产生了金那霉素来证实J1074。序列分析和一系列基因删除实验揭示了簇的边界，该簇跨越75 kb DNA。为了探查生物合成的最后一步，将激肽素F乙酰化为金那霉素D，基因敲除和互补实验确定了涉及最终乙酰化转化的单个基因产物。这项研究提供了来自S. galtieri Sgt26的kinamycin基因簇的完整遗传信息，并建立了异源生物合成作为继续对化合物形成和利用机理进行机械评估的生产平台。
更新日期：2018-01-17
中文翻译：
异源寄主链霉菌J1074内卡那霉素生物合成的重建
重氮芴化合物（如卡那霉素和洛麦维汀）具有独特的分子结构和引人注目的药用生物活性。然而，尚未完全阐明对该天然产物家族的生物合成细节的完全理解。另外，缺乏遗传和技术上适合的生产宿主限制了这些化合物的全部药用潜力。在这里，我们报告了通过细菌人工染色体克隆捕获了来自金链霉菌Sgt26的完整的金那霉素基因簇，并通过在异源宿主链霉菌中成功产生了金那霉素来证实J1074。序列分析和一系列基因删除实验揭示了簇的边界，该簇跨越75 kb DNA。为了探查生物合成的最后一步，将激肽素F乙酰化为金那霉素D，基因敲除和互补实验确定了涉及最终乙酰化转化的单个基因产物。这项研究提供了来自S. galtieri Sgt26的kinamycin基因簇的完整遗传信息，并建立了异源生物合成作为继续对化合物形成和利用机理进行机械评估的生产平台。
京公网安备 11010802027423号