Engineered biosynthesis and characterization of disaccharide-pimaricin
Abstract Background Disaccharide polyene macrolides exhibit superior water solubility and significantly reduced hemolytic toxicity compared to their monosaccharide counterparts, making them promising candidates for safer antifungal therapeutics. In this study, we engineered a Streptomyces gilvospore...
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BMC
2025-05-01
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| Series: | Microbial Cell Factories |
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| Online Access: | https://doi.org/10.1186/s12934-025-02742-9 |
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| author | Xiaoshan Zuo Liqin Qiao Yao Dong Xing Jin Zhongyuan Ren Hao Cui |
| author_facet | Xiaoshan Zuo Liqin Qiao Yao Dong Xing Jin Zhongyuan Ren Hao Cui |
| author_sort | Xiaoshan Zuo |
| collection | DOAJ |
| description | Abstract Background Disaccharide polyene macrolides exhibit superior water solubility and significantly reduced hemolytic toxicity compared to their monosaccharide counterparts, making them promising candidates for safer antifungal therapeutics. In this study, we engineered a Streptomyces gilvosporeus (pSET152-nppY) capable of producing disaccharide-pimaricin (DSP) through heterologous expression of the nppY gene, which encodes a glycosyltransferase responsible for the second sugar extension in the biosynthetic pathway. Results The novel compound was structurally characterized and designated disaccharide-pimaricin (DSP), featuring an aglycone identical to pimaricin and a unique disaccharide moiety (mycosaminyl-α1–4-N-acetylglucosamine). A purification protocol for DSP was established. Compared to pimaricin, DSP demonstrated a 50% reduction in antifungal activity, a 12.6-fold decrease in hemolytic toxicity, and a remarkable 107.6-fold increase in water solubility. Growth analysis revealed a delayed growth cycle in the mutant strain, suggesting that nppY expression may impose additional metabolic burden. Optimization of the fermentation medium using a statistical design identified an optimal formulation, with a maximum DSP titer of 138.168 mg/L. Conclusions This study underscores the potential of disaccharide polyene macrolides as safer antifungal agents and establishes a robust framework for engineering strains to produce these compounds. The findings provide critical insights into balancing biosynthetic efficiency and strain fitness, advancing the development of next-generation polyene antibiotics. |
| format | Article |
| id | doaj-art-72f1867592f14010a485bf520f1c4b46 |
| institution | OA Journals |
| issn | 1475-2859 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Microbial Cell Factories |
| spelling | doaj-art-72f1867592f14010a485bf520f1c4b462025-08-20T02:29:51ZengBMCMicrobial Cell Factories1475-28592025-05-0124111810.1186/s12934-025-02742-9Engineered biosynthesis and characterization of disaccharide-pimaricinXiaoshan Zuo0Liqin Qiao1Yao Dong2Xing Jin3Zhongyuan Ren4Hao Cui5School of Chemistry and Pharmaceutical Engineering, Jilin Institute of Chemical TechnologySchool of Chemistry and Pharmaceutical Engineering, Jilin Institute of Chemical TechnologyCollege of Biology & Food Engineering, Jilin Institute of Chemical TechnologyDepartment of Anesthesiology, Affiliated Hospital of Beihua University, Jilin Institute of Chemical TechnologyCollege of Biology & Food Engineering, Jilin Institute of Chemical TechnologySchool of Chemistry and Pharmaceutical Engineering, Jilin Institute of Chemical TechnologyAbstract Background Disaccharide polyene macrolides exhibit superior water solubility and significantly reduced hemolytic toxicity compared to their monosaccharide counterparts, making them promising candidates for safer antifungal therapeutics. In this study, we engineered a Streptomyces gilvosporeus (pSET152-nppY) capable of producing disaccharide-pimaricin (DSP) through heterologous expression of the nppY gene, which encodes a glycosyltransferase responsible for the second sugar extension in the biosynthetic pathway. Results The novel compound was structurally characterized and designated disaccharide-pimaricin (DSP), featuring an aglycone identical to pimaricin and a unique disaccharide moiety (mycosaminyl-α1–4-N-acetylglucosamine). A purification protocol for DSP was established. Compared to pimaricin, DSP demonstrated a 50% reduction in antifungal activity, a 12.6-fold decrease in hemolytic toxicity, and a remarkable 107.6-fold increase in water solubility. Growth analysis revealed a delayed growth cycle in the mutant strain, suggesting that nppY expression may impose additional metabolic burden. Optimization of the fermentation medium using a statistical design identified an optimal formulation, with a maximum DSP titer of 138.168 mg/L. Conclusions This study underscores the potential of disaccharide polyene macrolides as safer antifungal agents and establishes a robust framework for engineering strains to produce these compounds. The findings provide critical insights into balancing biosynthetic efficiency and strain fitness, advancing the development of next-generation polyene antibiotics.https://doi.org/10.1186/s12934-025-02742-9Streptomyces gilposporeusGlycosyltransferaseDisaccharide-pimaricinWater-solubleAntifungal activityHemolysis |
| spellingShingle | Xiaoshan Zuo Liqin Qiao Yao Dong Xing Jin Zhongyuan Ren Hao Cui Engineered biosynthesis and characterization of disaccharide-pimaricin Microbial Cell Factories Streptomyces gilposporeus Glycosyltransferase Disaccharide-pimaricin Water-soluble Antifungal activity Hemolysis |
| title | Engineered biosynthesis and characterization of disaccharide-pimaricin |
| title_full | Engineered biosynthesis and characterization of disaccharide-pimaricin |
| title_fullStr | Engineered biosynthesis and characterization of disaccharide-pimaricin |
| title_full_unstemmed | Engineered biosynthesis and characterization of disaccharide-pimaricin |
| title_short | Engineered biosynthesis and characterization of disaccharide-pimaricin |
| title_sort | engineered biosynthesis and characterization of disaccharide pimaricin |
| topic | Streptomyces gilposporeus Glycosyltransferase Disaccharide-pimaricin Water-soluble Antifungal activity Hemolysis |
| url | https://doi.org/10.1186/s12934-025-02742-9 |
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