Improvement of pristinamycin I (PI) production in Streptomyces pristinaespiralis by metabolic engineering approaches
Pristinamycin, produced by Streptomyces pristinaespiralis, which is a streptogramin-like antibiotic consisting of two chemically unrelated components: pristinamycin I (PI) and pristinamycin II (PII), shows potent activity against many antibiotic-resistant pathogens. However, so far pristinamycin pro...
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| Format: | Article |
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KeAi Communications Co., Ltd.
2017-06-01
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| Series: | Synthetic and Systems Biotechnology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405805X17300509 |
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| author | Jiali Meng Rongrong Feng Guosong Zheng Mei Ge Yvonne Mast Wolfgang Wohlleben Jufang Gao Weihong Jiang Yinhua Lu |
| author_facet | Jiali Meng Rongrong Feng Guosong Zheng Mei Ge Yvonne Mast Wolfgang Wohlleben Jufang Gao Weihong Jiang Yinhua Lu |
| author_sort | Jiali Meng |
| collection | DOAJ |
| description | Pristinamycin, produced by Streptomyces pristinaespiralis, which is a streptogramin-like antibiotic consisting of two chemically unrelated components: pristinamycin I (PI) and pristinamycin II (PII), shows potent activity against many antibiotic-resistant pathogens. However, so far pristinamycin production titers are still quite low, particularly those of PI. In this study, we constructed a PI single component producing strain by deleting the PII biosynthetic genes (snaE1 and snaE2). Then, two metabolic engineering approaches, including deletion of the repressor gene papR3 and chromosomal integration of an extra copy of the PI biosynthetic gene cluster (BGC), were employed to improve PI production. The final engineered strain ΔPIIΔpapR3/PI produced a maximum PI level of 132 mg/L, with an approximately 2.4-fold higher than that of the parental strain S. pristinaespiralis HCCB10218. Considering that the PI biosynthetic genes are clustered in two main regions in the 210 kb “supercluster” containing the PI and PII biosynthetic genes as well as a cryptic polyketide BGC, these two regions were cloned separately and then were successfully assembled into the PI BGC by the transformation-associated recombination (TAR) system. Collectively, the metabolic engineering approaches employed is very efficient for strain improvement in order to enhance PI titer. |
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| institution | Directory Open Access Journal |
| issn | 2405-805X |
| language | English |
| last_indexed | 2024-04-24T08:51:10Z |
| publishDate | 2017-06-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Synthetic and Systems Biotechnology |
| spelling | doaj.art-9533ce5450af4a11a72ae506587729c52024-04-16T11:58:49ZengKeAi Communications Co., Ltd.Synthetic and Systems Biotechnology2405-805X2017-06-012213013610.1016/j.synbio.2017.06.001Improvement of pristinamycin I (PI) production in Streptomyces pristinaespiralis by metabolic engineering approachesJiali Meng0Rongrong Feng1Guosong Zheng2Mei Ge3Yvonne Mast4Wolfgang Wohlleben5Jufang Gao6Weihong Jiang7Yinhua Lu8Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200032, ChinaKey Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200032, ChinaKey Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200032, ChinaShanghai Laiyi Center for Biopharmaceuticals R&D, Shanghai, 201203, ChinaMikrobiologie/Biotechnologie, Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Fakultät für Biologie, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 28, D-72076, Tübingen, GermanyMikrobiologie/Biotechnologie, Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Fakultät für Biologie, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 28, D-72076, Tübingen, GermanyShanghai Normal University, Shanghai, 200234, ChinaKey Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200032, ChinaKey Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200032, ChinaPristinamycin, produced by Streptomyces pristinaespiralis, which is a streptogramin-like antibiotic consisting of two chemically unrelated components: pristinamycin I (PI) and pristinamycin II (PII), shows potent activity against many antibiotic-resistant pathogens. However, so far pristinamycin production titers are still quite low, particularly those of PI. In this study, we constructed a PI single component producing strain by deleting the PII biosynthetic genes (snaE1 and snaE2). Then, two metabolic engineering approaches, including deletion of the repressor gene papR3 and chromosomal integration of an extra copy of the PI biosynthetic gene cluster (BGC), were employed to improve PI production. The final engineered strain ΔPIIΔpapR3/PI produced a maximum PI level of 132 mg/L, with an approximately 2.4-fold higher than that of the parental strain S. pristinaespiralis HCCB10218. Considering that the PI biosynthetic genes are clustered in two main regions in the 210 kb “supercluster” containing the PI and PII biosynthetic genes as well as a cryptic polyketide BGC, these two regions were cloned separately and then were successfully assembled into the PI BGC by the transformation-associated recombination (TAR) system. Collectively, the metabolic engineering approaches employed is very efficient for strain improvement in order to enhance PI titer.http://www.sciencedirect.com/science/article/pii/S2405805X17300509Streptomyces pristinaespiralisPristinamycin IBiosynthetic gene clusterMetabolic engineering |
| spellingShingle | Jiali Meng Rongrong Feng Guosong Zheng Mei Ge Yvonne Mast Wolfgang Wohlleben Jufang Gao Weihong Jiang Yinhua Lu Improvement of pristinamycin I (PI) production in Streptomyces pristinaespiralis by metabolic engineering approaches Synthetic and Systems Biotechnology Streptomyces pristinaespiralis Pristinamycin I Biosynthetic gene cluster Metabolic engineering |
| title | Improvement of pristinamycin I (PI) production in Streptomyces pristinaespiralis by metabolic engineering approaches |
| title_full | Improvement of pristinamycin I (PI) production in Streptomyces pristinaespiralis by metabolic engineering approaches |
| title_fullStr | Improvement of pristinamycin I (PI) production in Streptomyces pristinaespiralis by metabolic engineering approaches |
| title_full_unstemmed | Improvement of pristinamycin I (PI) production in Streptomyces pristinaespiralis by metabolic engineering approaches |
| title_short | Improvement of pristinamycin I (PI) production in Streptomyces pristinaespiralis by metabolic engineering approaches |
| title_sort | improvement of pristinamycin i pi production in streptomyces pristinaespiralis by metabolic engineering approaches |
| topic | Streptomyces pristinaespiralis Pristinamycin I Biosynthetic gene cluster Metabolic engineering |
| url | http://www.sciencedirect.com/science/article/pii/S2405805X17300509 |
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