A new-generation of Bacillus subtilis cell factory for further elevated scyllo-inositol production
Abstract Background A stereoisomer of inositol, scyllo-inositol (SI), has been regarded as a promising therapeutic agent for Alzheimer’s disease. However, this compound is relatively rare, whereas another stereoisomer of inositol, myo-inositol (MI) is abundant in nature. Bacillus subtilis 168 has th...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-04-01
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| Series: | Microbial Cell Factories |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12934-017-0682-0 |
| _version_ | 1811280520551596032 |
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| author | Kosei Tanaka Ayane Natsume Shu Ishikawa Shinji Takenaka Ken-ichi Yoshida |
| author_facet | Kosei Tanaka Ayane Natsume Shu Ishikawa Shinji Takenaka Ken-ichi Yoshida |
| author_sort | Kosei Tanaka |
| collection | DOAJ |
| description | Abstract Background A stereoisomer of inositol, scyllo-inositol (SI), has been regarded as a promising therapeutic agent for Alzheimer’s disease. However, this compound is relatively rare, whereas another stereoisomer of inositol, myo-inositol (MI) is abundant in nature. Bacillus subtilis 168 has the ability to metabolize inositol stereoisomers, including MI and SI. Previously, we reported a B. subtilis cell factory with modified inositol metabolism that converts MI into SI in the culture medium. The strain was constructed by deleting all genes related to inositol metabolism and overexpressing key enzymes, IolG and IolW. By using this strain, 10 g/l of MI initially included in the medium was completely converted into SI within 48 h of cultivation in a rich medium containing 2% (w/v) Bacto soytone. Results When the initial concentration of MI was increased to 50 g/l, conversion was limited to 15.1 g/l of SI. Therefore, overexpression systems of IolT and PntAB, the main transporter of MI in B. subtilis and the membrane-integral nicotinamide nucleotide transhydrogenase in Escherichia coli respectively, were additionally introduced into the B. subtilis cell factory, but the conversion efficiency hardly improved. We systematically determined the amount of Bacto soytone necessary for ultimate conversion, which was 4% (w/v). As a result, the conversion of SI reached to 27.6 g/l within 48 h of cultivation. Conclusions The B. subtilis cell factory was improved to yield a SI production rate of 27.6 g/l/48 h by simultaneous overexpression of IolT and PntAB, and by addition of 4% (w/v) Bacto soytone in the conversion medium. The concentration of SI was increased even in the stationary phase perhaps due to nutrients in the Bacto soytone that contribute to the conversion process. Thus, MI conversion to SI may be further optimized via identification and control of these unknown nutrients. |
| first_indexed | 2024-04-13T01:16:17Z |
| format | Article |
| id | doaj.art-207708cdd4034faea1f2c3d75b4d420e |
| institution | Directory Open Access Journal |
| issn | 1475-2859 |
| language | English |
| last_indexed | 2024-04-13T01:16:17Z |
| publishDate | 2017-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Microbial Cell Factories |
| spelling | doaj.art-207708cdd4034faea1f2c3d75b4d420e2022-12-22T03:08:54ZengBMCMicrobial Cell Factories1475-28592017-04-011611810.1186/s12934-017-0682-0A new-generation of Bacillus subtilis cell factory for further elevated scyllo-inositol productionKosei Tanaka0Ayane Natsume1Shu Ishikawa2Shinji Takenaka3Ken-ichi Yoshida4Organization of Advanced Science and Technology, Kobe UniversityGraduate School of Agricultural Science, Department of Agrobioscience, Kobe UniversityGraduate School of Science, Technology and Innovation, Department of Science, Technology and Innovation, Kobe UniversityGraduate School of Agricultural Science, Department of Agrobioscience, Kobe UniversityGraduate School of Science, Technology and Innovation, Department of Science, Technology and Innovation, Kobe UniversityAbstract Background A stereoisomer of inositol, scyllo-inositol (SI), has been regarded as a promising therapeutic agent for Alzheimer’s disease. However, this compound is relatively rare, whereas another stereoisomer of inositol, myo-inositol (MI) is abundant in nature. Bacillus subtilis 168 has the ability to metabolize inositol stereoisomers, including MI and SI. Previously, we reported a B. subtilis cell factory with modified inositol metabolism that converts MI into SI in the culture medium. The strain was constructed by deleting all genes related to inositol metabolism and overexpressing key enzymes, IolG and IolW. By using this strain, 10 g/l of MI initially included in the medium was completely converted into SI within 48 h of cultivation in a rich medium containing 2% (w/v) Bacto soytone. Results When the initial concentration of MI was increased to 50 g/l, conversion was limited to 15.1 g/l of SI. Therefore, overexpression systems of IolT and PntAB, the main transporter of MI in B. subtilis and the membrane-integral nicotinamide nucleotide transhydrogenase in Escherichia coli respectively, were additionally introduced into the B. subtilis cell factory, but the conversion efficiency hardly improved. We systematically determined the amount of Bacto soytone necessary for ultimate conversion, which was 4% (w/v). As a result, the conversion of SI reached to 27.6 g/l within 48 h of cultivation. Conclusions The B. subtilis cell factory was improved to yield a SI production rate of 27.6 g/l/48 h by simultaneous overexpression of IolT and PntAB, and by addition of 4% (w/v) Bacto soytone in the conversion medium. The concentration of SI was increased even in the stationary phase perhaps due to nutrients in the Bacto soytone that contribute to the conversion process. Thus, MI conversion to SI may be further optimized via identification and control of these unknown nutrients.http://link.springer.com/article/10.1186/s12934-017-0682-0Bacillus subtilisscyllo-inositolmyo-inositolBioconversionAlzheimer’s disease |
| spellingShingle | Kosei Tanaka Ayane Natsume Shu Ishikawa Shinji Takenaka Ken-ichi Yoshida A new-generation of Bacillus subtilis cell factory for further elevated scyllo-inositol production Microbial Cell Factories Bacillus subtilis scyllo-inositol myo-inositol Bioconversion Alzheimer’s disease |
| title | A new-generation of Bacillus subtilis cell factory for further elevated scyllo-inositol production |
| title_full | A new-generation of Bacillus subtilis cell factory for further elevated scyllo-inositol production |
| title_fullStr | A new-generation of Bacillus subtilis cell factory for further elevated scyllo-inositol production |
| title_full_unstemmed | A new-generation of Bacillus subtilis cell factory for further elevated scyllo-inositol production |
| title_short | A new-generation of Bacillus subtilis cell factory for further elevated scyllo-inositol production |
| title_sort | new generation of bacillus subtilis cell factory for further elevated scyllo inositol production |
| topic | Bacillus subtilis scyllo-inositol myo-inositol Bioconversion Alzheimer’s disease |
| url | http://link.springer.com/article/10.1186/s12934-017-0682-0 |
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