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Enhanced Production of 1-Deoxynojirimycin in Bacillus subtilis subsp. inaquosorum by Random Mutagenesis and Culture Optimization

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Abstract

1-Deoxynojirimycin (DNJ) is a potent inhibitor of α-glucosidase having antidiabetic and antiviral activities. In the present study, DNJ production by Bacillus subtilis subsp. inaquosorum KCTC 13429 (B. subtilis IWT) was confirmed and a mutant B. subtilis I.247 strain showing 52% increased DNJ production than wild-type strain after cultivation in 5% defatted soybean meal (DFS) for five days was isolated by UV random mutagenesis. The optimum culture conditions to maximize DNJ production by B. subtilis I.247 was predicted using response surface methodology to cultivate in medium containing 3.4% sorbitol and 2.4% yeast extract as carbon and nitrogen sources, respectively, at a temperature of 32°C. Under these conditions B. subtilis I.247 was able to produce 359 mg/L after five days of cultivation. Furthermore, when the B. subtilis I.247 transformant harboring a vector expressing a gabT1-yktc1-gutB1 DNJ biosynthetic gene cluster was cultured under the optimized condition, DNJ production was increased to 773 mg/L, representing a level 6.2-fold higher than that of the wild-type strain cultured in 5% DFS for five days.

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  • 13 May 2021

    The correct data in abstract is correct given in the PDF file, but tagged incorrectly in xml, 50% should be 52%.

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Acknowledgements

This work was supported by Grants from the Intelligent Synthetic Biology Global Frontier Program of the National Research Foundation and Korea Research Institute of Bioscience and Biotechnology (KRIBB) in Republic of Korea. We are very grateful to Dr. Woo-Jung Kim in the Gyeonggido Business & Science Accelerator Bio Center (Gyeonggido, Korea) for help with UHPLC-MS/MS analysis. We also appreciate Dr. Sang Yoon Kim for help with vector construction and Dr. Seung Wook Kim for his valuable comments.

The authors declare no conflict of interest.

Neither ethical approval nor informed consent was required for this study.

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  1. These authors contributed equally to this study.

Authors and Affiliations

  1. Environmental Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Korea

    Khai Ngoc Nguyen, Yunah Kim, Sawarot Maibunkaew, Jisoo Park, Mien Thi Nguyen & Doo-Byoung Oh

  2. Department of Biosystems and Bioengineering, KRIBB School of Biotechnology, University of Science and Technology (UST), Daejeon, 34113, Korea

    Khai Ngoc Nguyen, Yunah Kim, Sawarot Maibunkaew, Jisoo Park, Mien Thi Nguyen, Doo-Byoung Oh & Ohsuk Kwon

  3. SME Support Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Korea

    Ohsuk Kwon

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Nguyen, K.N., Kim, Y., Maibunkaew, S. et al. Enhanced Production of 1-Deoxynojirimycin in Bacillus subtilis subsp. inaquosorum by Random Mutagenesis and Culture Optimization. Biotechnol Bioproc E 26, 265–276 (2021). https://doi.org/10.1007/s12257-020-0231-2

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