Pathway and protein channel engineering of Bacillus subtilis for improved production of desthiobiotin and biotin
Biotin (vitamin B7) is a crucial cofactor for various metabolic processes and has significant applications in pharmaceuticals, cosmetics, and animal feed. Bacillus subtilis, a well-studied Gram-positive bacterium, presents a promising host for biotin production due to its Generally Recognized as Saf...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2025-03-01
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| Series: | Synthetic and Systems Biotechnology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405805X24001431 |
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| author | Yue Wu Guang-Qing Du Dong-Han Ma Jin-Long Li Huan Fang Hui-Na Dong Zhao-Xia Jin Da-Wei Zhang |
| author_facet | Yue Wu Guang-Qing Du Dong-Han Ma Jin-Long Li Huan Fang Hui-Na Dong Zhao-Xia Jin Da-Wei Zhang |
| author_sort | Yue Wu |
| collection | DOAJ |
| description | Biotin (vitamin B7) is a crucial cofactor for various metabolic processes and has significant applications in pharmaceuticals, cosmetics, and animal feed. Bacillus subtilis, a well-studied Gram-positive bacterium, presents a promising host for biotin production due to its Generally Recognized as Safe (GRAS) status, robust genetic tractability, and capacity for metabolite secretion. This study focuses on the metabolic engineering of B. subtilis to enhance biotin biosynthesis. Initially, the desthiobiotin (DTB) and biotin synthesis ability of different B. subtilis strains were evaluated to screen for suitable chassis cells. Subsequently, the titers of DTB and biotin were increased to 21.6 mg/L and 2.7 mg/L, respectively, by relieving the feedback repression of biotin synthesis and deleting the biotin uptake protein YhfU. Finally, through engineering the access tunnel to the active site of biotin synthase (BioB) for reactants and modulating its expression, the biotin titer was increased to 11.2 mg/L, marking an 1130-fold improvement compared to the wild-type strain. These findings provide novel strategies for enhancing the production of DTB and improving the conversion efficiency of DTB to biotin. |
| format | Article |
| id | doaj-art-75ca6c60ed334e1fbfe6761e5e40ab9e |
| institution | OA Journals |
| issn | 2405-805X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Synthetic and Systems Biotechnology |
| spelling | doaj-art-75ca6c60ed334e1fbfe6761e5e40ab9e2025-08-20T02:24:59ZengKeAi Communications Co., Ltd.Synthetic and Systems Biotechnology2405-805X2025-03-0110130731310.1016/j.synbio.2024.11.005Pathway and protein channel engineering of Bacillus subtilis for improved production of desthiobiotin and biotinYue Wu0Guang-Qing Du1Dong-Han Ma2Jin-Long Li3Huan Fang4Hui-Na Dong5Zhao-Xia Jin6Da-Wei Zhang7School of Biological Engineering, Dalian Polytechnic University, Dalian, China; Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China; National Technology Innovation Center of Synthetic Biology, Tianjin, China; Key Laboratory of Engineering Biology for Low-Carbon Manufacturing, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, ChinaTianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China; National Technology Innovation Center of Synthetic Biology, Tianjin, China; Key Laboratory of Engineering Biology for Low-Carbon Manufacturing, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, ChinaSchool of Biological Engineering, Dalian Polytechnic University, Dalian, China; Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China; National Technology Innovation Center of Synthetic Biology, Tianjin, China; Key Laboratory of Engineering Biology for Low-Carbon Manufacturing, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, ChinaTianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China; National Technology Innovation Center of Synthetic Biology, Tianjin, China; Key Laboratory of Engineering Biology for Low-Carbon Manufacturing, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, ChinaTianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China; National Technology Innovation Center of Synthetic Biology, Tianjin, China; Key Laboratory of Engineering Biology for Low-Carbon Manufacturing, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China; University of Chinese Academy of Sciences, Beijing, ChinaTianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China; National Technology Innovation Center of Synthetic Biology, Tianjin, China; Key Laboratory of Engineering Biology for Low-Carbon Manufacturing, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China; University of Chinese Academy of Sciences, Beijing, ChinaSchool of Biological Engineering, Dalian Polytechnic University, Dalian, China; Corresponding author.Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China; National Technology Innovation Center of Synthetic Biology, Tianjin, China; Key Laboratory of Engineering Biology for Low-Carbon Manufacturing, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China; University of Chinese Academy of Sciences, Beijing, China; Corresponding author. Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.Biotin (vitamin B7) is a crucial cofactor for various metabolic processes and has significant applications in pharmaceuticals, cosmetics, and animal feed. Bacillus subtilis, a well-studied Gram-positive bacterium, presents a promising host for biotin production due to its Generally Recognized as Safe (GRAS) status, robust genetic tractability, and capacity for metabolite secretion. This study focuses on the metabolic engineering of B. subtilis to enhance biotin biosynthesis. Initially, the desthiobiotin (DTB) and biotin synthesis ability of different B. subtilis strains were evaluated to screen for suitable chassis cells. Subsequently, the titers of DTB and biotin were increased to 21.6 mg/L and 2.7 mg/L, respectively, by relieving the feedback repression of biotin synthesis and deleting the biotin uptake protein YhfU. Finally, through engineering the access tunnel to the active site of biotin synthase (BioB) for reactants and modulating its expression, the biotin titer was increased to 11.2 mg/L, marking an 1130-fold improvement compared to the wild-type strain. These findings provide novel strategies for enhancing the production of DTB and improving the conversion efficiency of DTB to biotin.http://www.sciencedirect.com/science/article/pii/S2405805X24001431BiotinBacillus subtilisBiotin synthaseRibosomal binding site |
| spellingShingle | Yue Wu Guang-Qing Du Dong-Han Ma Jin-Long Li Huan Fang Hui-Na Dong Zhao-Xia Jin Da-Wei Zhang Pathway and protein channel engineering of Bacillus subtilis for improved production of desthiobiotin and biotin Synthetic and Systems Biotechnology Biotin Bacillus subtilis Biotin synthase Ribosomal binding site |
| title | Pathway and protein channel engineering of Bacillus subtilis for improved production of desthiobiotin and biotin |
| title_full | Pathway and protein channel engineering of Bacillus subtilis for improved production of desthiobiotin and biotin |
| title_fullStr | Pathway and protein channel engineering of Bacillus subtilis for improved production of desthiobiotin and biotin |
| title_full_unstemmed | Pathway and protein channel engineering of Bacillus subtilis for improved production of desthiobiotin and biotin |
| title_short | Pathway and protein channel engineering of Bacillus subtilis for improved production of desthiobiotin and biotin |
| title_sort | pathway and protein channel engineering of bacillus subtilis for improved production of desthiobiotin and biotin |
| topic | Biotin Bacillus subtilis Biotin synthase Ribosomal binding site |
| url | http://www.sciencedirect.com/science/article/pii/S2405805X24001431 |
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