Comparative genomic analysis of Streptomyces rapamycinicus NRRL 5491 and its mutant overproducing rapamycin
Abstract Streptomyces rapamycinicus NRRL 5491 is a well-known producer of rapamycin, a secondary metabolite with useful bioactivities, including antifungal, antitumor, and immunosuppressive functions. For the enhanced rapamycin production, a rapamycin-overproducing strain SRMK07 was previously obtai...
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| Format: | Article |
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Nature Portfolio
2022-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-14199-6 |
| _version_ | 1811343683552804864 |
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| author | Hee-Geun Jo Joshua Julio Adidjaja Do-Kyung Kim Bu-Soo Park Namil Lee Byung-Kwan Cho Hyun Uk Kim Min-Kyu Oh |
| author_facet | Hee-Geun Jo Joshua Julio Adidjaja Do-Kyung Kim Bu-Soo Park Namil Lee Byung-Kwan Cho Hyun Uk Kim Min-Kyu Oh |
| author_sort | Hee-Geun Jo |
| collection | DOAJ |
| description | Abstract Streptomyces rapamycinicus NRRL 5491 is a well-known producer of rapamycin, a secondary metabolite with useful bioactivities, including antifungal, antitumor, and immunosuppressive functions. For the enhanced rapamycin production, a rapamycin-overproducing strain SRMK07 was previously obtained as a result of random mutagenesis. To identify genomic changes that allowed the SRMK07 strain’s enhanced rapamycin production, genomes of the NRRL 5491 and SRMK07 strains were newly sequenced in this study. The resulting genome sequences of the wild-type and SRMK07 strains showed the size of 12.47 Mbp and 9.56 Mbp, respectively. Large deletions were observed at both end regions of the SRMK07 strain’s genome, which cover 17 biosynthetic gene clusters (BGCs) encoding secondary metabolites. Also, genes in a genomic region containing the rapamycin BGC were shown to be duplicated. Finally, comparative metabolic network analysis using these two strains’ genome-scale metabolic models revealed biochemical reactions with different metabolic fluxes, which were all associated with NADPH generation. Taken together, the genomic and computational approaches undertaken in this study suggest biological clues for the enhanced rapamycin production of the SRMK07 strain. These clues can also serve as a basis for systematic engineering of a production host for further enhanced rapamycin production. |
| first_indexed | 2024-04-13T19:33:08Z |
| format | Article |
| id | doaj.art-37a14f6883f64b1481b4d67393a2df1a |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T19:33:08Z |
| publishDate | 2022-06-01 |
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| spelling | doaj.art-37a14f6883f64b1481b4d67393a2df1a2022-12-22T02:33:07ZengNature PortfolioScientific Reports2045-23222022-06-0112111310.1038/s41598-022-14199-6Comparative genomic analysis of Streptomyces rapamycinicus NRRL 5491 and its mutant overproducing rapamycinHee-Geun Jo0Joshua Julio Adidjaja1Do-Kyung Kim2Bu-Soo Park3Namil Lee4Byung-Kwan Cho5Hyun Uk Kim6Min-Kyu Oh7Department of Chemical and Biological Engineering, Korea UniversityDepartment of Chemical and Biomolecular Engineering (BK21 Four), Korea Advanced Institute of Science and Technology (KAIST)Department of Chemical and Biological Engineering, Korea UniversityDepartment of Chemical and Biological Engineering, Korea UniversityDepartment of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST)Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST)Department of Chemical and Biomolecular Engineering (BK21 Four), Korea Advanced Institute of Science and Technology (KAIST)Department of Chemical and Biological Engineering, Korea UniversityAbstract Streptomyces rapamycinicus NRRL 5491 is a well-known producer of rapamycin, a secondary metabolite with useful bioactivities, including antifungal, antitumor, and immunosuppressive functions. For the enhanced rapamycin production, a rapamycin-overproducing strain SRMK07 was previously obtained as a result of random mutagenesis. To identify genomic changes that allowed the SRMK07 strain’s enhanced rapamycin production, genomes of the NRRL 5491 and SRMK07 strains were newly sequenced in this study. The resulting genome sequences of the wild-type and SRMK07 strains showed the size of 12.47 Mbp and 9.56 Mbp, respectively. Large deletions were observed at both end regions of the SRMK07 strain’s genome, which cover 17 biosynthetic gene clusters (BGCs) encoding secondary metabolites. Also, genes in a genomic region containing the rapamycin BGC were shown to be duplicated. Finally, comparative metabolic network analysis using these two strains’ genome-scale metabolic models revealed biochemical reactions with different metabolic fluxes, which were all associated with NADPH generation. Taken together, the genomic and computational approaches undertaken in this study suggest biological clues for the enhanced rapamycin production of the SRMK07 strain. These clues can also serve as a basis for systematic engineering of a production host for further enhanced rapamycin production.https://doi.org/10.1038/s41598-022-14199-6 |
| spellingShingle | Hee-Geun Jo Joshua Julio Adidjaja Do-Kyung Kim Bu-Soo Park Namil Lee Byung-Kwan Cho Hyun Uk Kim Min-Kyu Oh Comparative genomic analysis of Streptomyces rapamycinicus NRRL 5491 and its mutant overproducing rapamycin Scientific Reports |
| title | Comparative genomic analysis of Streptomyces rapamycinicus NRRL 5491 and its mutant overproducing rapamycin |
| title_full | Comparative genomic analysis of Streptomyces rapamycinicus NRRL 5491 and its mutant overproducing rapamycin |
| title_fullStr | Comparative genomic analysis of Streptomyces rapamycinicus NRRL 5491 and its mutant overproducing rapamycin |
| title_full_unstemmed | Comparative genomic analysis of Streptomyces rapamycinicus NRRL 5491 and its mutant overproducing rapamycin |
| title_short | Comparative genomic analysis of Streptomyces rapamycinicus NRRL 5491 and its mutant overproducing rapamycin |
| title_sort | comparative genomic analysis of streptomyces rapamycinicus nrrl 5491 and its mutant overproducing rapamycin |
| url | https://doi.org/10.1038/s41598-022-14199-6 |
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