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Bioconversion of vitamin D3 to calcifediol by using resting cells of Pseudonocardia sp.

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Abstract

Objectives

Resting cells of Pseudonocardia sp. KCTC 1029BP were used for the bioconversion of vitamin D3 to calcifediol which is widely used to treat osteomalacia and is industrially produced by chemical synthesis.

Results

To obtain the maximum bioconversion yield of calcifediol by the microbial conversion of vitamin D3, a two-step optimization process was used, including the Plackett–Burman and the central composite designs. Six variables, namely agitation speed, aeration rate, resting cell concentration, vitamin D3 concentration, temperature, and pH, were monitored. Of these, aeration rate, resting cell concentration, and temperature were selected as key variables for calcifediol production and were optimized using the central composite design. Optimal bioconversion conditions obtained were as follows: aeration rate of 0.2 vvm, resting cell concentration of 4.7 % w/v, and temperature of 33 °C.

Conclusion

Using the optimal conditions, 356 mg calcifediol l−1 was obtained with a bioconversion yield of 59.4 % in a 75 l fermentor. These are the highest values reported to date.

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References

  • Anderson MJ, Whitcomb PJ (2005) RSM simplified: optimizing processes using response surface methods for design of experiments. Productivity Press, Boca Raton

    Google Scholar 

  • Andrews DR, Barton DH, Hesse RH, Pechet MM (1986) Synthesis of 25-hydroxy-and 1 alpha., 25-dihydroxy vitamin D3 from vitamin D2 (calciferol). J Org Chem 51:4819–4828

    Article  CAS  Google Scholar 

  • Bar A, Rosenberg J, Perlman R, Hurwitz S (1987) Field rickets in turkeys: relationship to vitamin D. Poult Sci 66:68–72

    Article  CAS  PubMed  Google Scholar 

  • Brooks MH, Bell NH, Love L, Stern PH, Orfei E, Queener SF, Hamstra AJ, DeLuca HF (1978) Vitamin-D-dependent rickets type II: resistance of target organs to 1, 25-dihydroxyvitamin D. New Engl J Med 298:996–999

    Article  CAS  PubMed  Google Scholar 

  • Clements M, Johnson L, Fraser D (1987) A new mechanism for induced vitamin D deficiency in calcium deprivation. Nature 32:62–66

    Article  Google Scholar 

  • de Carvalho CC (2011) Enzymatic and whole cell catalysis: finding new strategies for old processes. Biotechnol Adv 29:75–83

    Article  PubMed  Google Scholar 

  • DeLuca HF, Schnoes HK (1983) Vitamin D: recent advances. Annu Rev Biochem 52:411–439

    Article  CAS  PubMed  Google Scholar 

  • Eisman J, Shepard R, DeLuca H (1977) Determination of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 in human plasma using high-pressure liquid chromatography. Anal Biochem 80:298–305

    Article  CAS  PubMed  Google Scholar 

  • Flores ER, Pérez F, de la Torre M (1997) Scale-up of Bacillus thuringiensis fermentation based on oxygen transfer. J Ferment Bioeng 83:561–564

    Article  CAS  Google Scholar 

  • Gangadharan D, Sivaramakrishnan S, Nampoothiri KM, Sukumaran RK, Pandey A (2008) Response surface methodology for the optimization of α amylase production by Bacillus amyloliquefaciens. Biores Technol 99:4597–4602

    Article  CAS  Google Scholar 

  • Hatakeyama S, Sugawara K, Numata H, Takano S (1991) A novel convergent synthesis of (+)-1α, 25-dihydroxyvitamin D3 using a chromium (II)-mediated coupling reaction. J Org Chem 56:461–463

    Article  CAS  Google Scholar 

  • Imoto N, Nishioka T, Tamura T (2011) Permeabilization induced by lipid II-targeting lantibiotic nisin and its effect on the bioconversion of vitamin D3 to 25-hydroxyvitamin D3 by Rhodococcus erythropolis. Biochem Biophys Res Commun 405:393–398

    Article  CAS  PubMed  Google Scholar 

  • Kametani T, Furuyama H (1987) Synthesis of vitamin D3 and related compounds. Med Res Rev 7:147–171

    Article  CAS  PubMed  Google Scholar 

  • Kang D, Lee H, Park J, Bang J, Hong S, Kim T (2006) Optimization of culture conditions for the bioconversion of vitamin D3 to 1α, 25-dihydroxyvitamin D3 using Pseudonocardia autotrophica ID 9302. Biotechnol Bioprocess Eng 11:408–413

    Article  CAS  Google Scholar 

  • Kang D, Im J, Kang J, Kim K (2015) Whole cell bioconversion of vitamin D3 to calcitriol using Pseudonocardia sp. KCTC 1029BP. Bioproc Biosyst Eng. doi:10.1007/s00449-015-1368-9

    Google Scholar 

  • Kulprecha S, Ueda T, Nihira T, Yoshida T, Taguchi H (1985) Optimum conditions for ursodeoxycholic acid production from lithocholic acid by Fusarium equiseti M41. Appl Environ Microbiol 49:338–344

    PubMed Central  CAS  PubMed  Google Scholar 

  • Lau J, Tran C, Licari P, Galazzo J (2004) Development of a high cell-density fed-batch bioprocess for the heterologous production of 6-deoxyerythronolide B in Escherichia coli. J Biotechnol 110:95–103

    Article  CAS  PubMed  Google Scholar 

  • Lund J, DeLuca HF (1966) Biologically active metabolite of vitamin D3 from bone, liver, and blood serum. J Lipid Res 7:739–744

    CAS  PubMed  Google Scholar 

  • Lythgoe B (1980) Simonsen Lecture. Synthetic approaches to vitamin D and its relatives. Chem Soc Rev 9:449–475

    Article  CAS  Google Scholar 

  • Madhok T, DeLuca H (1979) Characteristics of the rat liver microsomal enzyme system converting cholecalciferol into 25-hydroxycholecalciferol. Evidence for the participation of cytochrome p-450. Biochem J 184:491–499

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mandenius C, Brundin A (2008) Bioprocess optimization using design of experiments methodology. Biotechnol Prog 24:1191–1203

    Article  CAS  PubMed  Google Scholar 

  • Plackett R, Burman J (1946) The design of optimum multifactorial experiments. Biometrika 33:305–325

    Article  Google Scholar 

  • Raissi S, Farsani R (2009) Statistical process optimization through multi-response surface methodology. World Acad Sci Eng Technol 51:267–271

    Google Scholar 

  • Sasaki J, Mikami A, Mizoue K, Omura S (1991) Transformation of 25- and 1α-hydroxyvitamin D3 to 1α, 25-dihydroxyvitamin D3 by using Streptomyces sp. strains. Appl Environ Microbiol 57:2841–2846

    PubMed Central  CAS  PubMed  Google Scholar 

  • Sasaki J, Miyazaki A, Saito M, Adachi T, Mizoue K, Hanada K, Omura S (1992) Transformation of vitamin D3 to 1α, 25-dihydroxyvitamin D3 via 25-hydroxyvitamin D3 using Amycolata sp. strains. Appl Microbiol Biotechnol 38:152–157

    CAS  PubMed  Google Scholar 

  • Seino Y, Tanaka H, Yamaoka K, Yabuuchi H (1987) Circulating 1α, 25-dihydroxyvitamin D levels after a single dose of 1α, 25-dihydroxyvitamin D3 or 1α-hydroxyvitamin D3 in normal men. Bone Miner 2:479–485

    CAS  PubMed  Google Scholar 

  • Soares J, Kerr J, Gray R (1995) 25-hydroxycholecalciferol in poultry nutrition. Poult Sci 74:1919–1934

    Article  CAS  PubMed  Google Scholar 

  • Sreekumar G, Krishnan S (2010) Enhanced biomass production study on probiotic Bacillus subtilis SK09 by medium optimization using response surface methodology. Afr J Biotechnol 9:8078–8084

    CAS  Google Scholar 

  • Takeda K, Asou T, Matsuda A, Kimura K, Okamura K, Okamoto R, Sasaki J, Adachi T, Omura S (1994) Application of cyclodextrin to microbial transformation of vitamin D3 to 25-hydroxyvitamin D3 and 1α, 25-dihydroxyvitamin D3. J Ferment Bioeng 78:380–382

    Article  CAS  Google Scholar 

  • Uzura A, Katsuragi T, Tani Y (2001) Conversion of various aromatic compounds by resting cells of Fusarium moniliforme strain MS31. J Biosci Bioeng 92:381–384

    Article  CAS  PubMed  Google Scholar 

  • Vanmaele L, De Clercq P, Vandewalle M (1985) An efficient synthesis of 1α, 25-dihydroxy vitamin D3. Tetrahedron 41:141–144

    Article  CAS  Google Scholar 

  • Vieth R (1999) Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr 69:842–856

    CAS  PubMed  Google Scholar 

  • Wang Z, Zhuge J, Fang H, Prior B (2001) Glycerol production by microbial fermentation: a review. Biotechnol Adv 19:201–223

    Article  CAS  PubMed  Google Scholar 

  • Xiong Z, Tu X, Tu G (2008) Optimization of medium composition for actinomycin X2 production by Streptomyces spp. JAU4234 using response surface methodology. J Ind Microbiol Biotechnol 35:729–734

    Article  CAS  PubMed  Google Scholar 

  • Yasutake Y, Nishioka T, Imoto N, Tamura T (2013) A single mutation at the ferredoxin binding site of p450 Vdh enables efficient biocatalytic production of 25 hydroxyvitamin D3. ChemBioChem 14:2284–2291

    Article  CAS  PubMed  Google Scholar 

  • Yee L, Blanch H (1993) Defined media optimization for growth of recombinant Escherichia coli X90. Biotechnol Bioeng 41:221–230

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

KHK acknowledges the Grant support by the Ministry of Trade, Industry & Energy (10048684) and the facility support at the Korea University Food Safety Hall for the Institute of Biomedical Science and Food Safety.

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Correspondence to Kyoung Heon Kim.

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Kang, DJ., Im, JH., Kang, JH. et al. Bioconversion of vitamin D3 to calcifediol by using resting cells of Pseudonocardia sp.. Biotechnol Lett 37, 1895–1904 (2015). https://doi.org/10.1007/s10529-015-1862-9

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  • DOI: https://doi.org/10.1007/s10529-015-1862-9

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