Puromycin A, B and C, cryptic nucleosides identified from Streptomyces alboniger NRRL B-1832 by PPtase-based activation
Natural product discovery is pivot for drug development, however, this endeavor is often challenged by the wide inactivation or silence of natural products biosynthetic pathways. We recently developed a highly efficient approach to activate cryptic/silenced biosynthetic pathways through augmentation...
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| Format: | Article |
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KeAi Communications Co., Ltd.
2018-03-01
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| Series: | Synthetic and Systems Biotechnology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405805X17300844 |
| _version_ | 1797204949994569728 |
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| author | Xiaoli Yan Benyin Zhang Wenya Tian Qi Dai Xiaoqin Zheng Ke Hu Xinxin Liu Zixin Deng Xudong Qu |
| author_facet | Xiaoli Yan Benyin Zhang Wenya Tian Qi Dai Xiaoqin Zheng Ke Hu Xinxin Liu Zixin Deng Xudong Qu |
| author_sort | Xiaoli Yan |
| collection | DOAJ |
| description | Natural product discovery is pivot for drug development, however, this endeavor is often challenged by the wide inactivation or silence of natural products biosynthetic pathways. We recently developed a highly efficient approach to activate cryptic/silenced biosynthetic pathways through augmentation of the phosphopantetheinylation of carrier proteins. By applying this approach in the Streptomyces alboniger NRRL B-1832, we herein identified three cryptic nucleosides products, including one known puromycin A and two new derivatives (puromycin B and C). The biosynthesis of these products doesn't require the involvement of carrier protein, indicating the phosphopantetheinyl transferase (PPtase) indeed plays a fundamental regulatory role in metabolites biosynthesis. These results demonstrate that the PPtase-based approach have a much broader effective scope than the previously assumed carrier protein-involving pathways, which will benefit future natural products discovery and biosynthetic studies. |
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| institution | Directory Open Access Journal |
| issn | 2405-805X |
| language | English |
| last_indexed | 2024-04-24T08:43:22Z |
| publishDate | 2018-03-01 |
| publisher | KeAi Communications Co., Ltd. |
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| series | Synthetic and Systems Biotechnology |
| spelling | doaj.art-851a0ed08a534b828862f04b84c5c60f2024-04-16T14:45:26ZengKeAi Communications Co., Ltd.Synthetic and Systems Biotechnology2405-805X2018-03-0131768010.1016/j.synbio.2018.02.001Puromycin A, B and C, cryptic nucleosides identified from Streptomyces alboniger NRRL B-1832 by PPtase-based activationXiaoli Yan0Benyin Zhang1Wenya Tian2Qi Dai3Xiaoqin Zheng4Ke Hu5Xinxin Liu6Zixin Deng7Xudong Qu8Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, ChinaState Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, ChinaKey Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, ChinaKey Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, ChinaKey Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, ChinaKey Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, ChinaKey Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, ChinaKey Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, ChinaKey Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, ChinaNatural product discovery is pivot for drug development, however, this endeavor is often challenged by the wide inactivation or silence of natural products biosynthetic pathways. We recently developed a highly efficient approach to activate cryptic/silenced biosynthetic pathways through augmentation of the phosphopantetheinylation of carrier proteins. By applying this approach in the Streptomyces alboniger NRRL B-1832, we herein identified three cryptic nucleosides products, including one known puromycin A and two new derivatives (puromycin B and C). The biosynthesis of these products doesn't require the involvement of carrier protein, indicating the phosphopantetheinyl transferase (PPtase) indeed plays a fundamental regulatory role in metabolites biosynthesis. These results demonstrate that the PPtase-based approach have a much broader effective scope than the previously assumed carrier protein-involving pathways, which will benefit future natural products discovery and biosynthetic studies.http://www.sciencedirect.com/science/article/pii/S2405805X17300844PuromycinPhosphopantetheinyl transferaseGene activationStreptomyces albonigerGenome mining |
| spellingShingle | Xiaoli Yan Benyin Zhang Wenya Tian Qi Dai Xiaoqin Zheng Ke Hu Xinxin Liu Zixin Deng Xudong Qu Puromycin A, B and C, cryptic nucleosides identified from Streptomyces alboniger NRRL B-1832 by PPtase-based activation Synthetic and Systems Biotechnology Puromycin Phosphopantetheinyl transferase Gene activation Streptomyces alboniger Genome mining |
| title | Puromycin A, B and C, cryptic nucleosides identified from Streptomyces alboniger NRRL B-1832 by PPtase-based activation |
| title_full | Puromycin A, B and C, cryptic nucleosides identified from Streptomyces alboniger NRRL B-1832 by PPtase-based activation |
| title_fullStr | Puromycin A, B and C, cryptic nucleosides identified from Streptomyces alboniger NRRL B-1832 by PPtase-based activation |
| title_full_unstemmed | Puromycin A, B and C, cryptic nucleosides identified from Streptomyces alboniger NRRL B-1832 by PPtase-based activation |
| title_short | Puromycin A, B and C, cryptic nucleosides identified from Streptomyces alboniger NRRL B-1832 by PPtase-based activation |
| title_sort | puromycin a b and c cryptic nucleosides identified from streptomyces alboniger nrrl b 1832 by pptase based activation |
| topic | Puromycin Phosphopantetheinyl transferase Gene activation Streptomyces alboniger Genome mining |
| url | http://www.sciencedirect.com/science/article/pii/S2405805X17300844 |
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