Characterization of Pathway-Specific Regulator NigR for High Yield Production of Nigericin in <i>Streptomyces malaysiensis</i> F913
Nigericin is a polyether antibiotic with potent antibacterial, antifungal, antimalarial and anticancer activity. NigR, the only regulator in the nigericin biosynthetic gene cluster in <i>Streptomyces malaysiensis</i> F913, was identified as a SARP family regulator. Disruption of <i>...
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MDPI AG
2022-07-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/11/7/938 |
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| author | Junhong Wei Mengting Ma Senwen Guo Yaobo Xu Jie Xie Guoqing Pan Zeyang Zhou |
| author_facet | Junhong Wei Mengting Ma Senwen Guo Yaobo Xu Jie Xie Guoqing Pan Zeyang Zhou |
| author_sort | Junhong Wei |
| collection | DOAJ |
| description | Nigericin is a polyether antibiotic with potent antibacterial, antifungal, antimalarial and anticancer activity. NigR, the only regulator in the nigericin biosynthetic gene cluster in <i>Streptomyces malaysiensis</i> F913, was identified as a SARP family regulator. Disruption of <i>nigR</i> abolished nigericin biosynthesis, while complementation of <i>nigR</i> restored nigericin production, suggesting that NigR is an essential positive regulator for nigericin biosynthesis. Overexpression of <i>nigR</i> in <i>Streptomyces malaysiensis</i> led to significant increase in nigericin production compared to the wild-type strain. Nigericin production in the overexpression strain was found to reach 0.56 g/L, which may be the highest nigericin titer reported to date. Transcriptional analysis suggested that <i>nigR</i> is required for the transcription of structural genes in the <i>nig</i> gene cluster; quantitative RT-PCR analysis revealed that the expression of structural genes was upregulated in the <i>nigR</i> overexpression strain. Our study suggested that NigR acts in a positive manner to modulate nigericin production by activating transcription of structural genes and provides an effective strategy for scaling up nigericin production. |
| first_indexed | 2024-03-09T12:19:36Z |
| format | Article |
| id | doaj.art-270b0061fca54b6197c3d2f292f5fbc5 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-09T12:19:36Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
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| series | Antibiotics |
| spelling | doaj.art-270b0061fca54b6197c3d2f292f5fbc52023-11-30T22:41:33ZengMDPI AGAntibiotics2079-63822022-07-0111793810.3390/antibiotics11070938Characterization of Pathway-Specific Regulator NigR for High Yield Production of Nigericin in <i>Streptomyces malaysiensis</i> F913Junhong Wei0Mengting Ma1Senwen Guo2Yaobo Xu3Jie Xie4Guoqing Pan5Zeyang Zhou6State Key Laboratory of Silkworm Genome Biology, Chongqing Key Laboratory of Microsporidia Infection and Control, Southwest University, Chongqing 400715, ChinaCollege of Sericulture, Textile and Biomass Sciences, Southwest University, Chongqing 400715, ChinaState Key Laboratory of Silkworm Genome Biology, Chongqing Key Laboratory of Microsporidia Infection and Control, Southwest University, Chongqing 400715, ChinaSchool of Life Sciences, Southwest University, Chongqing 400715, ChinaState Key Laboratory of Silkworm Genome Biology, Chongqing Key Laboratory of Microsporidia Infection and Control, Southwest University, Chongqing 400715, ChinaState Key Laboratory of Silkworm Genome Biology, Chongqing Key Laboratory of Microsporidia Infection and Control, Southwest University, Chongqing 400715, ChinaState Key Laboratory of Silkworm Genome Biology, Chongqing Key Laboratory of Microsporidia Infection and Control, Southwest University, Chongqing 400715, ChinaNigericin is a polyether antibiotic with potent antibacterial, antifungal, antimalarial and anticancer activity. NigR, the only regulator in the nigericin biosynthetic gene cluster in <i>Streptomyces malaysiensis</i> F913, was identified as a SARP family regulator. Disruption of <i>nigR</i> abolished nigericin biosynthesis, while complementation of <i>nigR</i> restored nigericin production, suggesting that NigR is an essential positive regulator for nigericin biosynthesis. Overexpression of <i>nigR</i> in <i>Streptomyces malaysiensis</i> led to significant increase in nigericin production compared to the wild-type strain. Nigericin production in the overexpression strain was found to reach 0.56 g/L, which may be the highest nigericin titer reported to date. Transcriptional analysis suggested that <i>nigR</i> is required for the transcription of structural genes in the <i>nig</i> gene cluster; quantitative RT-PCR analysis revealed that the expression of structural genes was upregulated in the <i>nigR</i> overexpression strain. Our study suggested that NigR acts in a positive manner to modulate nigericin production by activating transcription of structural genes and provides an effective strategy for scaling up nigericin production.https://www.mdpi.com/2079-6382/11/7/938nigericin<i>Streptomyces malaysiensis</i>NigRpathway-specific regulator |
| spellingShingle | Junhong Wei Mengting Ma Senwen Guo Yaobo Xu Jie Xie Guoqing Pan Zeyang Zhou Characterization of Pathway-Specific Regulator NigR for High Yield Production of Nigericin in <i>Streptomyces malaysiensis</i> F913 Antibiotics nigericin <i>Streptomyces malaysiensis</i> NigR pathway-specific regulator |
| title | Characterization of Pathway-Specific Regulator NigR for High Yield Production of Nigericin in <i>Streptomyces malaysiensis</i> F913 |
| title_full | Characterization of Pathway-Specific Regulator NigR for High Yield Production of Nigericin in <i>Streptomyces malaysiensis</i> F913 |
| title_fullStr | Characterization of Pathway-Specific Regulator NigR for High Yield Production of Nigericin in <i>Streptomyces malaysiensis</i> F913 |
| title_full_unstemmed | Characterization of Pathway-Specific Regulator NigR for High Yield Production of Nigericin in <i>Streptomyces malaysiensis</i> F913 |
| title_short | Characterization of Pathway-Specific Regulator NigR for High Yield Production of Nigericin in <i>Streptomyces malaysiensis</i> F913 |
| title_sort | characterization of pathway specific regulator nigr for high yield production of nigericin in i streptomyces malaysiensis i f913 |
| topic | nigericin <i>Streptomyces malaysiensis</i> NigR pathway-specific regulator |
| url | https://www.mdpi.com/2079-6382/11/7/938 |
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