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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Mo, SangJoon Lee, Sung-Kwon Jin, Ying-Yu Suh, Joo-Won |
| Description | Author Affiliation: Mo S ( Clinical Trial Institute, Biosafety & Validation Center, Dankook University, Choenan 31116, Republic of Korea.); Lee SK ( Division of Bioscience and Bioinformatics, Myongji University, Youngin 17058, Republic of Korea.); Jin YY ( Division of Bioscience and Bioinformatics, Myongji University, Youngin 17058, Republic of Korea.); Suh JW ( Division of Bioscience and Bioinformatics, Myongji University, Youngin 17058, Republic of Korea.) |
| Abstract | FK506, a widely used immunosuppressant, is a 23-membered polyketide macrolide that is produced by several Streptomyces species. FK506 high-yielding strain Streptomyces sp. RM7011 was developed from the discovered Streptomyces sp. KCCM 11116P by random mutagenesis in our previous study. The results of transcript expression analysis showed that the transcription levels of tcsA, B, C, and D were increased in Streptomyces sp. RM7011 by 2.1-, 3.1-, 3.3-, and 4.1- fold, respectively, compared with Streptomyces sp. KCCM 11116P. The overexpression of tcsABCD genes in Streptomyces sp. RM7011 gave rise to approximately 2.5-fold (238.1 µg/ml) increase in the level of FK506 production compared with that of Streptomyces sp. RM7011. When vinyl pentanoate was added into the culture broth of Streptomyces sp. RM7011, the level of FK506 production was approximately 2.2-fold (207.7 µg/ml) higher than that of the unsupplemented fermentation. Furthermore, supplementing the culture broth of Streptomyces sp. RM7011 expressing tcsABCD genes with vinyl pentanoate resulted in an additional 1.7-fold improvement in the FK506 titer (498.1 µg/ml) compared with that observed under nonsupplemented condition. Overall, the level of FK506 production was increased approximately 5.2-fold by engineering the supply of allylmalonyl-CoA in the high-yielding strain Streptomyces sp. RM7011, using a combination of overexpressing tcsABCD genes and adding vinyl pentanoate, as compared with Streptomyces sp. RM7011 (95.3 µg/ml). Moreover, among the three precursors analyzed, pentanoate was the most effective precursor, supporting the highest titer of FK506 in the FK506 high-yielding strain Streptomyces sp. RM7011. |
| File Format | HTM / HTML |
| ISSN | 10177825 |
| e-ISSN | 17388872 |
| Journal | Journal of Microbiology and Biotechnology |
| Issue Number | 2 |
| Volume Number | 26 |
| Language | English |
| Publisher | Korean Society for Microbiology and Biotechnology |
| Publisher Date | 2016-02-01 |
| Publisher Place | Korea (South) |
| Access Restriction | Open |
| Subject Keyword | Discipline Microbiology Discipline Biotechnology Immunosuppressive Agents Metabolism Malonyl Coenzyme A Genetics Streptomyces Tacrolimus Allyl Compounds Culture Media Chemistry Gene Expression Regulation, Bacterial Genes, Bacterial Genetic Engineering Isolation & Purification Malonates Multigene Family Mutagenesis Real-time Polymerase Chain Reaction Enzymology Growth & Development Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine Applied Microbiology and Biotechnology Biotechnology |
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