Improving Geldanamycin Production in <i>Streptomyces geldanamycininus</i> Through UV Mutagenesis of Protoplast
Geldanamycin, a benzoquinone ansa antibiotic, has been extensively applied in medical, agricultural, and health research areas due to its antitumor, antifungal, herbicidal, and antiradiation effects. In this study, an improvement of geldanamycin production by <i>Streptomyces geldanamycininus&l...
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2025-01-01
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| author | Yuan Yuan Lu Yang Zhikai Fang Haimin Chen Fei Sun Hong Jiang Jian Zhou |
| author_facet | Yuan Yuan Lu Yang Zhikai Fang Haimin Chen Fei Sun Hong Jiang Jian Zhou |
| author_sort | Yuan Yuan |
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| description | Geldanamycin, a benzoquinone ansa antibiotic, has been extensively applied in medical, agricultural, and health research areas due to its antitumor, antifungal, herbicidal, and antiradiation effects. In this study, an improvement of geldanamycin production by <i>Streptomyces geldanamycininus</i> FIM18-0592 was first performed by protoplasts combined with UV mutagenesis and ribosome engineering technology, respectively. The results showed that strains induced by UV mutagenesis of protoplasts were superior to protoplasts treated with erythromycin in terms of the positive variability, average relative titer, and maximum relative titer, with values of 51.95%, 99%, and 136%, respectively. A mutant strain that produced 3742 μg/mL geldanamycin was generated by protoplast UV mutagenesis, with a 36% higher yield than the initial strain. Multi-omic analysis revealed that the high-yielding geldanamycin in mutant strain 53 could upregulate <i>GdmG</i> and <i>GdmX</i> by 1.59 and 2.38 times in the ansamycin synthesis pathway, and downregulate <i>pks12</i>, <i>pikAI</i>, and <i>pikAII</i> by 0.25, 0.37, and 0.48 times in the fatty acid synthesis pathway, which was crucial for geldanamycin production. Our study provides a novel <i>S. geldanamycininus</i> geldanamycin production strategy and offers valuable insights for mutagenesis and breeding of other microorganisms. |
| format | Article |
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| institution | Kabale University |
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| spelling | doaj-art-b64eaa0bb12d45188a96b44f62fdecaf2025-01-24T13:42:58ZengMDPI AGMicroorganisms2076-26072025-01-0113118610.3390/microorganisms13010186Improving Geldanamycin Production in <i>Streptomyces geldanamycininus</i> Through UV Mutagenesis of ProtoplastYuan Yuan0Lu Yang1Zhikai Fang2Haimin Chen3Fei Sun4Hong Jiang5Jian Zhou6Fujian Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, 25 Jinbu Road, Fuzhou 350007, ChinaFujian Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, 25 Jinbu Road, Fuzhou 350007, ChinaFujian Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, 25 Jinbu Road, Fuzhou 350007, ChinaFujian Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, 25 Jinbu Road, Fuzhou 350007, ChinaFujian Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, 25 Jinbu Road, Fuzhou 350007, ChinaFujian Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, 25 Jinbu Road, Fuzhou 350007, ChinaFujian Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, 25 Jinbu Road, Fuzhou 350007, ChinaGeldanamycin, a benzoquinone ansa antibiotic, has been extensively applied in medical, agricultural, and health research areas due to its antitumor, antifungal, herbicidal, and antiradiation effects. In this study, an improvement of geldanamycin production by <i>Streptomyces geldanamycininus</i> FIM18-0592 was first performed by protoplasts combined with UV mutagenesis and ribosome engineering technology, respectively. The results showed that strains induced by UV mutagenesis of protoplasts were superior to protoplasts treated with erythromycin in terms of the positive variability, average relative titer, and maximum relative titer, with values of 51.95%, 99%, and 136%, respectively. A mutant strain that produced 3742 μg/mL geldanamycin was generated by protoplast UV mutagenesis, with a 36% higher yield than the initial strain. Multi-omic analysis revealed that the high-yielding geldanamycin in mutant strain 53 could upregulate <i>GdmG</i> and <i>GdmX</i> by 1.59 and 2.38 times in the ansamycin synthesis pathway, and downregulate <i>pks12</i>, <i>pikAI</i>, and <i>pikAII</i> by 0.25, 0.37, and 0.48 times in the fatty acid synthesis pathway, which was crucial for geldanamycin production. Our study provides a novel <i>S. geldanamycininus</i> geldanamycin production strategy and offers valuable insights for mutagenesis and breeding of other microorganisms.https://www.mdpi.com/2076-2607/13/1/186whole-genome sequencingtranscriptome sequencingprotoplast mutagenesisUV mutagenesisgeldanamycin |
| spellingShingle | Yuan Yuan Lu Yang Zhikai Fang Haimin Chen Fei Sun Hong Jiang Jian Zhou Improving Geldanamycin Production in <i>Streptomyces geldanamycininus</i> Through UV Mutagenesis of Protoplast Microorganisms whole-genome sequencing transcriptome sequencing protoplast mutagenesis UV mutagenesis geldanamycin |
| title | Improving Geldanamycin Production in <i>Streptomyces geldanamycininus</i> Through UV Mutagenesis of Protoplast |
| title_full | Improving Geldanamycin Production in <i>Streptomyces geldanamycininus</i> Through UV Mutagenesis of Protoplast |
| title_fullStr | Improving Geldanamycin Production in <i>Streptomyces geldanamycininus</i> Through UV Mutagenesis of Protoplast |
| title_full_unstemmed | Improving Geldanamycin Production in <i>Streptomyces geldanamycininus</i> Through UV Mutagenesis of Protoplast |
| title_short | Improving Geldanamycin Production in <i>Streptomyces geldanamycininus</i> Through UV Mutagenesis of Protoplast |
| title_sort | improving geldanamycin production in i streptomyces geldanamycininus i through uv mutagenesis of protoplast |
| topic | whole-genome sequencing transcriptome sequencing protoplast mutagenesis UV mutagenesis geldanamycin |
| url | https://www.mdpi.com/2076-2607/13/1/186 |
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