Whole cell bioconversion of vitamin D<inf>3</inf> to calcitriol using Pseudonocardia sp. KCTC 1029BP

Dae Jung Kang, Jong Hyuk Im, Jae Hoon Kang, Kyoung Heon Kim

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Abstract Calcitriol is an important drug used for treating osteoporosis, which can be produced from vitamin D<inf>3</inf>. The current method of producing calcitriol from vitamin D<inf>3</inf> 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 D<inf>3</inf> 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 D<inf>3</inf>. 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 MgSO<inf>4</inf>, 0.08 % β-cyclodextrin, 0.1 % NaCl, 0.2 % K<inf>2</inf>HPO<inf>4</inf>, and 0.03 % MnCl<inf>2</inf>. Using this optimal bioconversion medium, 61.87 mg/L of calcitriol, corresponding to a 30.94 % mass yield from vitamin D<inf>3</inf>, 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, K<inf>2</inf>HPO<inf>4</inf>, and MnCl<inf>2</inf>. In conclusion, utilizing whole cells of Pseudonocardia sp. KCTC 1029BP together with the optimal bioconversion medium markedly enhanced the production of calcitriol from vitamin D<inf>3</inf>.

Original languageEnglish
Article number1368
Pages (from-to)1281-1290
Number of pages10
JournalBioprocess and Biosystems Engineering
Volume38
Issue number7
DOIs
Publication statusPublished - 2015 Jul 1

Fingerprint

Bioconversion
Calcitriol
Cholecalciferol
Vitamins
Cyclodextrins
Tromethamine
Purification
Succinic Acid
Bioreactors
Sodium
Osteoporosis
Salts
Buffers
Catalysts
Metals
Costs and Cost Analysis
Chemical analysis

Keywords

  • Biocatalysis
  • Calcifediol
  • Calcitriol
  • Pseudonocardia sp.
  • Vitamin D<inf>3</inf>

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering

Cite this

Whole cell bioconversion of vitamin D<inf>3</inf> to calcitriol using Pseudonocardia sp. KCTC 1029BP. / Kang, Dae Jung; Im, Jong Hyuk; Kang, Jae Hoon; Kim, Kyoung Heon.

In: Bioprocess and Biosystems Engineering, Vol. 38, No. 7, 1368, 01.07.2015, p. 1281-1290.

Research output: Contribution to journalArticle

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abstract = "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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AU - Im, Jong Hyuk

AU - Kang, Jae Hoon

AU - Kim, Kyoung Heon

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N2 - 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.

AB - 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.

KW - Biocatalysis

KW - Calcifediol

KW - Calcitriol

KW - Pseudonocardia sp.

KW - Vitamin D<inf>3</inf>

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