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Production and application of menaquinone-7 (vitamin K2): a new perspective

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Abstract

Menaquinone-7, a highly valuable member of the vitamin K series, has significant effects on preventing osteoporosis and cardiovascular disease besides its positive effects on blood coagulation. In this review, chemical and biological aspects of menaquinone-7 are briefly summarized followed by a critical review on upstream and downstream processing developments for its production and recovery, including solid versus liquid fermentations, static versus agitated fermentations and online versus post-production recovery. Latest research outcomes for improving industrial scale production of menaquinone-7 are summarized and recommendations are given for areas of future research.

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References

  • Benedetti A, Daly S, Xaiz R, Pagani H (2009) A process for the preparation of vitamin K2. European Patent 20070154998

  • Bentley R, Meganathan R (1982) Biosynthesis of vitamin K (menaquinone) in bacteria. Microbiol Rev 46(3):241–280

    CAS  Google Scholar 

  • Berenjian A, Mahanama R, Talbot A, Biffin R, Regtop H, Valtchev P et al (2011) Efficient media for high menaquinone-7 production: response surface methodology approach. New Biotechnol 28(6):665–672. doi:10.1016/j.nbt.2011.07.007

    Article  CAS  Google Scholar 

  • Berenjian A, Mahanama R, Talbot A, Regtop H, Kavanagh J, Dehghani F (2012) Advances in menaquinone-7 production by bacillus subtilis natto: fed-batch glycerol addition. Am J Biochem Biotechnol 8(2):105–110. doi:10.3844/ajbbsp.2012.105.110

    Article  CAS  Google Scholar 

  • Berenjian A, Chan NL-C, Mahanama R, Talbot A, Regtop H, Kavanagh J, Dehghani F (2013) Effect of biofilm formation by Bacillus subtilis natto on menaquinone-7 biosynthesis. Mol Biotechnol 54(2):371–378. doi:10.1007/s12033-012-9576-x

    Article  CAS  Google Scholar 

  • Berenjian A, Mahanama R, Kavanagh J, Dehghani F (2015) Vitamin K series: current status and future prospects. Crit Rev Biotechnol  35(2):199–208. doi:10.3109/07388551.2013.832142

    Article  Google Scholar 

  • Berenjian A, Mahanama R, Talbot A, Regtop H, Kavanagh J, Dehghani F (2014) Designing of an intensification process for biosynthesis and recovery of menaquinone-7. Appl Biochem Biotechnol 172(3):1347–1357. doi:10.1007/s12010-013-0602-7

    Article  CAS  Google Scholar 

  • Binkley SB, Maccorquodale DW, Thayer A, Doisy EA (1939) The isolation of vitamin K1. J Biol Chem 130:219–234

    CAS  Google Scholar 

  • Cheng K-C, Demirci A, Catchmark JM (2010) Effects of plastic composite support and pH profiles on pullulan production in a biofilm reactor. Appl Microbiol Biotechnol 86(3):853–861. doi:10.1007/s00253-009-2332-x

    Article  CAS  Google Scholar 

  • Dam H (1935) The antihaemorrhagic vitamin of the chick: occurrence and chemical nature. Nature 135:652–653

    Article  CAS  Google Scholar 

  • Davidson RT, Foley AL, Engelke JA, Suttie JW (1998) Conversion of dietary phylloquinone to tissue menaquinone-4 in rats is not dependent on gut bacteria. J Nutr 128(2):220–223

    CAS  Google Scholar 

  • Ebrahiminezhad A, Varma V, Yang S, Berenjian A (2016) Magnetic immobilization of Bacillus subtilis natto cells for menaquinone-7 fermentation. Appl Microbiol Biotechnol 100(1):173–180. doi:10.1007/s00253-015-6977-3

    Article  CAS  Google Scholar 

  • Ercan D, Demirci A (2013a) Current and future trends for biofilm reactors for fermentation processes. Crit Rev Biotechnol 8551:1–14. doi:10.3109/07388551.2013.793170

    Google Scholar 

  • Ercan D, Demirci A (2013b) Production of human lysozyme in biofilm reactor and optimization of growth parameters of Kluyveromyces lactis K7. Appl Microbiol Biotechnol 97(14):6211–6221. doi:10.1007/s00253-013-4944-4

    Article  CAS  Google Scholar 

  • Gast GCM, de Roos NM, Sluijs I, Bots ML, Beulens JWJ, Geleijnse JM et al (2009) A high menaquinone intake reduces the incidence of coronary heart disease. Nutr Metab Cardiovasc Diseases 19(7):504–510. doi:10.1016/j.numecd.2008.10.004

    Article  CAS  Google Scholar 

  • Geleijnse JM, Vermeer C, Grobbee DE, Schurgers LJ, Knapen MHJ, van der Meer IM et al (2004) Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam study. J Nutr 134(11):3100–3105

    CAS  Google Scholar 

  • Ghildyal NP, Ramakrishna M, Lonsane BK, Karanth NG, Krishnaiah MM (1993) Temperature variations and amyloglucosidase levels at different bed depths in a solid state fermentation system. Chem Eng J 51(2):B17–B23. doi:10.1016/0300-9467(93)80019-K

    Article  CAS  Google Scholar 

  • Goodman SR, Marrs BL, Narconis RJ, Olson RE (1976) Isolation and description of a menaquinone mutant from Bacillus licheniformis. J Bacteriol 125(1):282–289

    CAS  Google Scholar 

  • Haddock BA, Jones CW (1977) Bacterial respiration. Bacteriol Rev 41(1):47–99

    CAS  Google Scholar 

  • Howard LM, Payne AG (2006) Health benefits of vitamin K2: a revolutionary natural treatment for heart disease and bone loss. In: Anderson J (ed), 1st edn. Basic Health Publications, Inc., Laguna Beach

  • Khiyami MA, Pometto ALI, Kennedy WJ (2006) Ligninolytic enzyme production by Phanerochaete chrysosporium in plastic composite support biofilm stirred tank bioreactors. J Agric Food Chem 54:1693–1698

    Article  CAS  Google Scholar 

  • Krishna C (2005) Solid-state fermentation systems—an overview. Crit Rev Biotechnol 25(1–2):1–30. doi:10.1080/07388550590925383

    Article  CAS  Google Scholar 

  • Lieberman S, Bruning NP (1990) The real vitamin and mineral book: a definitive guide to designing your personal supplement program, 3rd edn. Avery Group, New York

    Google Scholar 

  • Mahanama R, Berenjian A, Valtchev P, Talbot A, Biffin R, Regtop H et al (2011) Enhanced production of menaquinone 7 via solid substrate fermentation from Bacillus subtilis. Int J Food Eng 7(5):1–23. doi:10.2202/1556-3758.2314

    Article  Google Scholar 

  • Malathi S, Chakraborty R (1991) Production of alkaline protease by a new Aspergillus flavus isolate under solid-substrate fermentation conditions for use as a depilation agent. Appl Environ Microbiol 57(3):712–716

    CAS  Google Scholar 

  • Maton A (1993) Human biology and health, 1st edn. Prentice Hall, Englewood Cliffs

    Google Scholar 

  • Mitchell DA, Krieger N, Stuart DM, Pandey A (2000) New developments in solid-state fermentation II. Rational approaches to the design, operation and scale-up of bioreactors. Process Biochem 35(10):1211–1225. doi:10.1016/S0032-9592(00)00157-6

    Article  CAS  Google Scholar 

  • Morikawa M, Oogo Y, Yoshio S (2011) Method for producing quinones. US20110027844

  • Morishita T, Tamura N, Makino T, Kudo S (1999) Production of menaquinones by lactic acid bacteria. J Dairy Sci 82(9):1897–1903. doi:10.3168/jds.S0022-0302(99)75424-X

    Article  CAS  Google Scholar 

  • Pandey A (2003) Solid-state fermentation. Biochem Eng J 13(2–3):81–84. doi:10.1016/S1369-703X(02)00121-3

    Article  CAS  Google Scholar 

  • Perry RH (2007) Perry’s chemical engineers’ handbook, 8th edn. McGraw-Hill, New York

    Google Scholar 

  • Pongtharangkul T, Demirci A (2006) Effects of fed-batch fermentation and pH profiles on nisin production in suspended-cell and biofilm reactors. Appl Microbiol Biotechnol 73(1):73–79. doi:10.1007/s00253-006-0459-6

    Article  CAS  Google Scholar 

  • Puri A, Iqubal M, Zafar R, Panda BP (2015) Influence of physical, chemical and inducer treatments on menaquinone-7 biosynthesis by Bacillus subtilis MTCC 2756. Songklanakarin J Sci Technol 37(3):283–289

    CAS  Google Scholar 

  • Sato T, Yamada Y, Ohtani Y, Mitsui N, Murasawa H, Araki S (2001) Production of menaquinone (vitamin K2)-7 by Bacillus subtilis. J Biosci Bioeng 91(1):16–20

    Article  CAS  Google Scholar 

  • Schurgers LJ, Vermeer C (2001) Determination of phylloquinone and menaquinones in food effect of food matrix on circulating vitamin K concentrations. Pathophysiol Haemost Thromb 30(6):298–307

    Article  Google Scholar 

  • Schurgers LJ, Teunissen KJF, Hamulyák K, Knapen MHJ, Vik H, Vermeer C (2007) Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and Natto-derived menaquinone-7. Blood 109(8):3279–3283. doi:10.1182/blood-2006-08-040709

    Article  CAS  Google Scholar 

  • Shearer MJ, Newman P (2008) Metabolism and cell biology of vitamin K. Thromb Haemost 100:530–547. doi:10.1160/TH08-03-0147

    CAS  Google Scholar 

  • Singh R, Puri A, Panda BP (2015) Development of menaquinone-7 enriched nutraceutical: inside into medium engineering and process modeling. J Food Sci Technol 52(8):5212–5219. doi:10.1007/s13197-014-1600-7

    Article  CAS  Google Scholar 

  • Stahmann KP, Revuelta JL, Seulberger H (2000) Three biotechnical processes using Ashbya gossypii, Candida famata, or Bacillus subtilis compete with chemical riboflavin production. Appl Microbiol Biotechnol 53(5):509–516. doi:10.1007/s002530051649

    Article  CAS  Google Scholar 

  • Sumi H (2004) Edible compositions of Bacillus subtilis natto cells containing water-soluble vitamin K. US Patent 6677141

  • Suttie JW (1995) The importance of menaquinones in human Nutrition. Annu Rev Nutr 15:399–417. doi:10.1146/annurev.nu.15.070195.002151

    Article  CAS  Google Scholar 

  • Takenaka T, Inoue S, Takenaka Y, Matsumoto H, Fujii A (2002) Effects of vitamin K2 (menaquinone-7) from fermented okara on ALPase activity of human dental pulp. J Jpn Soc Food Sci Technol 49(5):348–352

    Article  CAS  Google Scholar 

  • Tani Y, Taguchi H (1989) Extracellular production of MK4 by a mutant of flavobacterium sp. 238-7 with a detergent-supplemented culture. J Ferment Bioeng 67(2):102–106

    Article  CAS  Google Scholar 

  • Tsukamoto Y, Kasai M, Kakuda H (2001) Construction of a Bacillus subtilis (natto) with high productivity of vitamin K2 (menaquinone-7) by analog resistance. Biosci Biotechnol Biochem 65(9):2007–2015

    Article  CAS  Google Scholar 

  • Uyar F, Baysal Z (2004) Production and optimization of process parameters for alkaline protease production by a newly isolated Bacillus sp. under solid state fermentation. Process Biochem 39(12):1893–1898. doi:10.1016/j.procbio.2003.09.016

    Article  CAS  Google Scholar 

  • Weber P (2001) Vitamin K and bone health. Nutrition 17(10):880–887. doi:10.1016/S0899-9007(01)00709-2

    Article  CAS  Google Scholar 

  • Widhalm JR, Ducluzeau A-L, Buller NE, Elowsky CG, Olsen LJ, Basset GJC (2012) Phylloquinone (vitamin K(1)) biosynthesis in plants: two peroxisomal thioesterases of Lactobacillales origin hydrolyze 1,4-dihydroxy-2-naphthoyl-CoA. Plant J: Cell Mol Biol 71(2):205–215. doi:10.1111/j.1365-313X.2012.04972.x

    Article  CAS  Google Scholar 

  • Wu W-J, Ahn B-Y (2011) Improved menaquinone (vitamin K2) production in Cheonggukjang by optimization of the fermentation conditions. Food Sci Biotechnol 20(6):1585–1591. doi:10.1007/s10068-011-0219-y

    Article  CAS  Google Scholar 

  • Wu CH, Chou CC (2009) Enhancement of aglycone, vitamin K2 and superoxide dismutase activity of black soybean through fermentation with Bacillus subtilis BCRC 14715 at different temperatures. J Agric Food Chem 57(22):10695–10700. doi:10.1021/jf902752t

    Article  CAS  Google Scholar 

  • Xu H, Lee H-Y, Ahn J (2011) Characteristics of biofilm formation by selected foodborne pathogens. J Food Saf 31(1):91–97. doi:10.1111/j.1745-4565.2010.00271.x

    Article  Google Scholar 

  • Yamaguchi M (2006) Regulatory mechanism of food factors in bone metabolism and prevention of osteoporosis. Yakugaku Zasshi 126(11):1117–1137. doi:10.1248/yakushi.126.1117

    Article  CAS  Google Scholar 

  • Yang ST (2007) Bioprocessing for value-added products from renewable resources: new technologies and applications. In: Yang ST (ed), 1st edn. Elsevier, Amsterdam

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Authors and Affiliations

  1. Department of Agricultural and Biological Engineering, The Pennsylvania State University, University Park, PA, 16802, USA

    Ehsan Mahdinia & Ali Demirci

  2. Faculty of Science and Engineering, The University of Waikato, Hamilton, 3240, New Zealand

    Aydin Berenjian

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  1. Ehsan Mahdinia
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  2. Ali Demirci
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  3. Aydin Berenjian
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Correspondence to Aydin Berenjian.

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Mahdinia, E., Demirci, A. & Berenjian, A. Production and application of menaquinone-7 (vitamin K2): a new perspective. World J Microbiol Biotechnol 33, 2 (2017). https://doi.org/10.1007/s11274-016-2169-2

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