Precursor engineering and cell physiological regulation for high level rapamycin production by Streptomyces hygroscopicus
Open accessAbstract
A process for high level production of rapamycin by Streptomyces hygroscopicus using statistical designs and feeding strategy was developed. The amino acids (i.e. Lys, Tyr, and Gln) for precursor supply were screened out in the initial phase of fermentation. The optimum levels determined with Box-Behnken design were Lys 20, Tyr 4, and Gln 3 g/l. In the rapamycin biosynthesis phase, the important component, ammonium sulphate, was also identified. A novel two-stage feeding strategy was developed successfully to increase the flux of rapamycin biosynthesis, in which the optimized amino acid components were fed in the initial phase of fermentation, and then switched to feed 2 g/l ammonium sulphate at 72 h. The maximal rapamycin production reached 860.6 mg/l in a 7 l fermentor, which was 182 % higher than that of the control. This was the first report to integrate precursor engineering and cell physiological regulation methods to optimize rapamycin production.
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The bioreactor rapamycin titer is 52% higher than the latest maximum value reported in the literature.
“which is 52 % higher than the latest maximum value reported in the literature.”
From Kinetics of rapamycin production by Streptomyces hygroscopicus MTCC 4003 (2014) · cites this paper as Zou and Li 2013
Table 5 (shown under Conclusion; page unavailable) lists 860.6 mg/l for this study and 783 mg/l as the highest titer among the earlier studies it compares. That is about 10% higher, not 52%. The Results section reports a different comparison: 182% higher than this study’s control. (LLM, conf=0.91)
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- Authors
- Zou, X., & Li, J.
- Affiliations
- Southwest University (CN)
- Corresponding author
- Zou, Xiang
- ORCID
- Venue
- Annals of Microbiology
- Published
- 2013-01-06
- Volume
- 63
- Issue
- 4
- Pages
- 1371-1378
- ISSN
- 0003-4649 (ISSN-L)
- 1590-4261
- 1869-2044
- OpenAlex
- W2013705148
- Cited by
- 13
- References
- 32
- Citations by year
- 2024: 2 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 1 · 2017: 2 · 2016: 1 · 2013: 1
- FWCI
- 0.49
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Annals of Microbiology (publishedVersion)
- Funders
- Southwest University
- Topics
- Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Microbial Metabolism and Applications
- Keywords
- Streptomyces hygroscopicus, precursor design, amino acid supplementation, lysine, tyrosine, glutamine, ammonium sulfate, fermentation optimization, Box-Behnken design, secondary metabolite biosynthesis
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