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Whole cell bioconversion of vitamin D3 to calcitriol using Pseudonocardia sp. KCTC 1029BP

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Abstract

Calcitriol is an important drug used for treating osteoporosis, which can be produced from vitamin D3. The current method of producing calcitriol from vitamin D3 during cultivation of microbial cells results in low yields of calcitriol and high purification costs. Therefore, in this study, the steps of cell cultivation and bioconversion of vitamin D3 to calcitriol were separated. Cells of Pseudonocardia sp. KCTC 1029BP were utilized as a whole cell catalyst to produce a high level and yield of calcitriol from vitamin D3. In addition, the effects of bioconversion buffers, cyclodextrins, and metal salts on the production of calcitriol were comparatively examined and selected for incorporation in the bioconversion medium, and their compositions were statistically optimized. The optimal bioconversion medium was determined as consisting of 15 mM Trizma base, 25 mM sodium succinate, 2 mM MgSO4, 0.08 % β-cyclodextrin, 0.1 % NaCl, 0.2 % K2HPO4, and 0.03 % MnCl2. Using this optimal bioconversion medium, 61.87 mg/L of calcitriol, corresponding to a 30.94 % mass yield from vitamin D3, was produced in a 75-L fermentor after 9 days. This calcitriol yield was 3.6 times higher than that obtained using a bioconversion medium lacking β-cyclodextrin, NaCl, K2HPO4, and MnCl2. In conclusion, utilizing whole cells of Pseudonocardia sp. KCTC 1029BP together with the optimal bioconversion medium markedly enhanced the production of calcitriol from vitamin D3.

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Acknowledgments

KHK acknowledges the grant support from the Advanced Biomass R&D Center of Korea (2011-0031353) funded by the Korean Government (MSIP) and the facility support at the Korea University Food Safety Hall for the Institute of Biomedical Science and Food Safety.

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Authors and Affiliations

  1. Department of Biotechnology, Korea University Graduate School, Seoul, 136-713, Republic of Korea

    Dae-Jung Kang & Kyoung Heon Kim

  2. Research Laboratories, Ildong Pharmaceutical, Hwaseong, 445-170, Republic of Korea

    Dae-Jung Kang, Jong-Hyuk Im & Jae-Hoon Kang

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  1. Dae-Jung Kang
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Correspondence to Kyoung Heon Kim.

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Kang, DJ., Im, JH., Kang, JH. et al. Whole cell bioconversion of vitamin D3 to calcitriol using Pseudonocardia sp. KCTC 1029BP. Bioprocess Biosyst Eng 38, 1281–1290 (2015). https://doi.org/10.1007/s00449-015-1368-9

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  • DOI: https://doi.org/10.1007/s00449-015-1368-9

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