Abstract
Menaquinone-7 (MK-7) is the most potent subtype of vitamin K with extraordinarily high half-life in the circulatory system. Therefore, MK-7 plays a critical role in promoting human wellbeing today. Studies on MK-7 every year show more and more magnificent benefits of it in preventing cardiovascular diseases and osteoporosis to battling cancer cells, Alzheimer’s and Parkinson’s diseases. Thus, it needs to be supplemented to daily diet for accumulative and long-term benefits. Chemical synthesis of MK-7 produces a significant cis-isomer form of it, which has no biological activity. Fortunately, due to its key role in electron transfer in bacteria, trans-MK-7 is biosynthesized by especially Gram-positive strains mainly Bacillus genus. Concordantly, MK-7 could be produced via solid or liquid state fermentation strategies. In either regime, when static fermentation is applied in the absence of agitation and aeration, operational issues arise such as heat and mass transfer inefficiencies. Thus, scaling up the process becomes a challenge. On the other hand, studies have indicated that biofilm and pellicle formation that occur in static fermentations are key characteristics for extracellular MK-7 secretion. Therefore, this review covers the most recent discoveries of the therapeutic properties of MK-7 and optimization attempts at increasing its biosynthesis in different media compositions and effective growth parameters as well as the cutting-edge use of biofilm reactors where B. subtilis cells have the infrastructures to form mature biofilm formations on plastic composite supports. Biofilm reactors therefore can provide robust extracellular MK-7 secretion while simultaneously enduring high agitation and aeration rates, which then address the scale-up and operational issues associated with static fermentation strategies.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bentley R, Meganathan R (1982) Biosynthesis of vitamin K (menaquinone) in bacteria. Microbiol Rev 46:241–280
Berenjian A, Mahanama R, Talbot A, Biffin R, Regtop H, Valtchev P, Kavanagh J, Dehghani F (2011) Efficient media for high menaquinone-7 production: response surface methodology approach. New Biotechnol 28:665–672. https://doi.org/10.1016/j.nbt.2011.07.007
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 8:105–110. https://doi.org/10.3844/ajbbsp.2012.105.110
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 54:371–378. https://doi.org/10.1007/s12033-012-9576-x
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 172:1347–1357. https://doi.org/10.1007/s12010-013-0602-7
Berenjian A, Mahanama R, Kavanagh J, Dehghani F (2015) Vitamin K series: current status and future prospects. Crit Rev Biotechnol 35:199–208. https://doi.org/10.3109/07388551.2013.832142
Beulens JW, Booth SL, van den Heuvel EG, Stoecklin E, Baka A, Vermeer C (2013) The role of menaquinones (vitamin K 2) in human health. Br J Nutr 110(8):1357–1368. https://doi.org/10.1017/S0007114513001013
Bhatt PC, Pathak S, Kumar V, Panda BP (2018) Attenuation of neurobehavioral and neurochemical abnormalities in animal model of cognitive deficits of Alzheimer’s disease by fermented soybean nanonutraceutical. Inflammopharmacology 26(1):105–118. https://doi.org/10.1007/s10787-017-0381-9
Binkley SB, Maccorquodale DW, Thayer A, Doisy EA (1939) The Isolation of Vitamin K1. J Biol Chem 130:219–234
Blencke HM, Homuth G, Ludwig H, Mäder U, Hecker M, Stülke J (2003) Transcriptional profiling of gene expression in response to glucose in Bacillus subtilis: regulation of the central metabolic pathways. Metab Eng 5(2):133–149. https://doi.org/10.1016/S1096-7176(03)00009-0
Blume SW, Curtis JR (2011) Medical costs of osteoporosis in the elderly medicare population. Osteoporos Int 22:1835–1844. https://doi.org/10.1007/s00198-010-1419-7
Booth SL (2012) Vitamin K: food composition and dietary intakes. Food Nutr Res 56(1):5505. https://doi.org/10.3402/fnr.v56i0.5505
Branda SS, Vik S, Friedman L, Kolter R (2005) Biofilms: the matrix revisited. Trends Microbiol 13:20–26. https://doi.org/10.1016/j.tim.2004.11.006
Burmulle M, Webb JS, Rao D, Hansen LH, Surensen SJ, Kjelleberg S (2006) Enhanced biofilm formation and increased resistance to antimicrobial agents and bacterial invasion are caused by synergistic interactions in multispecies biofilms. Appl Environ Microbiol 72:3916–3923. https://doi.org/10.1128/AEM.03022-05
Bresson JL, Flynn A, Heinonen M, Hulshof K, Korhonen H, Lagiou P, Løvik M, Marchelli R, Martin A, Moseley B and Palou A, (2009) Scientific Opinion on the substantiation of health claims related to vitamin K and maintenance of bone (ID 123, 127, 128, and 2879), blood coagulation (ID 124 and 126), and function of the heart and blood vessels (ID 124, 125 and 2880) pursuant to Article 13 (1) of Regulation (EC) No 1924/2006: Scientific Opinion of the Panel on Dietetic Products, Nutrition and Allergies. EFSA J 7(10)(1228). https://doi.org/10.2903/j.efsa.2009.1228
Chatake T, Yanagisawa Y, Inoue R, Sugiyama M, Matsuo T, Fujiwara S, Ohsugi T, Sumi H (2018) Purification and structural characterization of water-soluble menaquinone-7 produced by Bacillus subtilis natto. J Food Biochem 42(6):e12630. https://doi.org/10.1111/jfbc.12630
Cheng KC, Demirci A, Catchmark JM (2010) Advances in biofilm reactors for production of value-added products. Appl Microbiol Biotechnol 87(2):445–456. https://doi.org/10.1007/s00253-010-2622-3
Cho YH, Song JY, Kim KM, Kim MK, Lee IY, Kim SB, Kim HS, Han NS, Lee BH, Kim BS (2010) Production of nattokinase by batch and fed-batch culture of Bacillus subtilis. New Biotechnol 27(4):341–346. https://doi.org/10.1016/j.nbt.2010.06.003
Dam H (1935) The antihaemorrhagic vitamin of the chick: occurrence and chemical nature. Nature 135:652–653
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 128:220–223
Deepak V, Kalishwaralal K, Ramkumarpandian S, Venkatesh Babu S, Senthilkumar SR and Sangiliyandi G (2008) Optimization of media composition for Nattokinase production by Bacillus subtilis using response surface methodology. Bioresour Technol 99(17):8170-8174. https://doi.org/10.1016/j.biortech.2008.03.018
Dragh MA, Xu Z, Al-Allak ZS, Hong L (2017) Vitamin K2 prevents lymphoma in drosophila. Sci Rep 7(1):17047. https://doi.org/10.1038/s41598-017-17270-9
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. https://doi.org/10.1007/s00253-015-6977-3
Ercan D, Demirci A (2013) Current and future trends for biofilm reactors for fermentation processes. Crit Rev Biotechnol 8551:1–14. https://doi.org/10.3109/07388551.2013.793170
Fang Z, Wang L, Zhao G, Liu H, Wei H, Wang H, Ni W, Zheng Z, Wang P (2019) A simple and efficient preparative procedure for menaquinone-7 from Bacillus subtilis (natto) using two-stage extraction followed by microporous resins. Process Biochem In Press. https://doi.org/10.1016/j.procbio.2019.05.008
Fisher SH (1999) Microreview regulation of nitrogen metabolism in Bacillus subtilis. Mol Microbiol 32:223–232. https://doi.org/10.1046/j.1365-2958.1999.01333.x
Gast GCM, de Roos NM, Sluijs I, Bots ML, Beulens JWJ, Geleijnse JM, Witteman CJ, Grobbee DE, Peeters PHM, van der Schouw YT (2009) A high menaquinone intake reduces the incidence of coronary heart disease. Nutr Metab Cardiovasc Dis 19(7):504–510. https://doi.org/10.1016/j.numecd.2008.10.004
Geleijnse JM, Vermeer C, Grobbee DE, Schurgers LJ, Knapen MHJ, van der Meer IM, Hofman A, Witteman JCM (2004) Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. J Nutr 134(11):3100–3105
Goodman SR, Marrs BL, Narconis RJ, Olson RE (1976) Isolation and description of a menaquinone mutant from Bacillus licheniformis. J Bacteriol 125:282–289
Haddock BA, Jones CW (1977) Bacterial Respiration. Bacteriol Rev 41(1):47–99.
Ho KL, Pometto AL, Hinz PN, Dickson JS, Demirci A (1997) Ingredient selection for plastic composite supports for l-(1)-lactic acid biofilm fermentation by Lactobacillus casei subsp. rhamnosus. Appl Environ Microbiol 63:2516–2523
Howard LM, Payne AG (2006) Health benefits of vitamin k2: a revolutionary natural treatment for heart disease and bone loss, 1st edn. Basic Health Publications, Inc., Laguna Beach
Hu XC, Liu WM, Luo MM, Ren LJ, Ji XJ, Huang H (2017) Enhancing menaquinone-7 production by Bacillus natto R127 through the nutritional factors and surfactant. Appl Biochem Biotechnol 182(4):1630–1641. https://doi.org/10.1007/s12010-017-2423-6
Ikeda H, Doi Y (1990) A vitamin-K2-binding factor secreted from Bacillus subtilis. Eur J Biochem 192:219–224. https://doi.org/10.1111/j.1432-1033.1990.tb19218.x
Ivanova D, Zhelev Z, Getsov P, Nikolova B, Aoki I, Higashi T, Bakalova R (2018) Vitamin K: redox-modulation, prevention of mitochondrial dysfunction and anticancer effect. Redox Biol 16:352–358. https://doi.org/10.1016/j.redox.2018.03.013
Kuchma SL, O’Toole GA (2000) Surface-induced and biofilm-induced changes in gene expression. Curr Opin Biotechnol 11:429–433. https://doi.org/10.1016/S0958-1669(00)00123-3
Łaszcz M, Trzcińska K, Kubiszewski M, Krajewski K (2018) Structural and physicochemical studies of two key intermediates and the impurity in the new synthesis route of vitamin MK-7. J Mol Struct 1160:304–310. https://doi.org/10.1016/j.molstruc.2018.02.018
Li Z, Zhao G, Liu H, Guo Y, Wu H, Sun X, Wu X, Zheng Z (2017) Biotransformation of menadione to its prenylated derivative MK-3 using recombinant Pichia pastoris. J Ind Microbiol Biotechnol 44:973–985. https://doi.org/10.1007/s10295-017-1931-2
Lieberman S, Bruning NP (2007) The Real Vitamin and Mineral Book: A Definitive Guide to Designing Your Personal Supplement Program, 4th edn. Penguin: New York, NY, USA
Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, Ferguson TB, Ford E, Furie K, Gillespie C (2010) Executive summary: heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation 121:948–954. https://doi.org/10.1161/circulationaha.109.192666
Luo MM, Ren LJ, Chen SL, Ji XJ, Huang H (2016) Effect of media components and morphology of Bacillus natto on menaquinone-7 synthesis in submerged fermentation. Biotechnol Bioprocess Eng 21(6):777–786. https://doi.org/10.1007/s12257-016-0202-9
Mahanama R, Berenjian A, Valtchev P, Talbot A, Biffin R, Regtop H, Dehghani F, Kavanagh JM (2011) Enhanced production of menaquinone 7 via solid substrate fermentation from Bacillus subtilis. Int J Food Eng. https://doi.org/10.2202/1556-3758.2314
Mahanama R, Berenjian A, Regtop H, Talbot A, Dehghani F, Kavanagh JM (2012) Modeling menaquinone 7 production in tray type solid state fermenter. ANZIAM J 53:354–372. https://doi.org/10.21914/anziamj.v53i0.5103
Mahdinia E, Demirci A, Berenjian A (2017a) Production and application of menaquinone-7 (vitamin K2): a new perspective. World J Microbiol Biotechnol 33:2. https://doi.org/10.1007/s11274-016-2169-2
Mahdinia E, Demirci A, Berenjian A (2017b) Strain and plastic composite support (PCS) selection for vitamin K (menaquinone-7) production in biofilm reactors. Bioprocess Biosyst Eng 40:1507–1517. https://doi.org/10.1007/s00449-017-1807-x
Mahdinia E, Demirci A, Berenjian A (2018a) Optimization of Bacillus subtilis natto growth parameters in glycerol-based medium for vitamin K (menaquinone-7) production in biofilm reactors. Bioprocess Biosyst Eng 41:195–204. https://doi.org/10.1007/s00449-017-1857-0
Mahdinia E, Demirci A, Berenjian A (2018b) Utilization of glucose-based medium and optimization of Bacillus subtilis natto growth parameters for vitamin K (menaquinone-7) production in biofilm reactors. Biocatal Agric Biotechnol 13:219–224. https://doi.org/10.1016/j.bcab.2017.12.009
Mahdinia E, Demirci A, Berenjian A (2018c) Enhanced vitamin k (menaquinone-7) production by Bacillus subtilis natto in biofilm reactors by optimization of glucose-based medium. J Curr Pharm Biotechnol 19(11):917–924. https://doi.org/10.2174/1389201020666181126120401
Mahdinia E, Demirci A, Berenjian A (2018d) Implementation of fed-batch strategies for vitamin K (menaquinone-7) production by Bacillus subtilis natto in biofilm reactors. Appl Microbiol Biotechnol 102(21):9147–9157. https://doi.org/10.1007/s00253-018-9340-7
Mahdinia E, Demirci A, Berenjian A (2019a) Effects of medium components in a glycerol-based medium on vitamin K (menaquinone-7) production by Bacillus subtilis natto in biofilm reactors. Bioprocess Biosyst Eng 42(2):223–232. https://doi.org/10.1007/s00449-018-2027-8
Mahdinia E, Demirci A, Berenjian A (2019b) Modeling of vitamin K (Menaquinoe-7) fermentation by Bacillus subtilis natto in biofilm reactors. Biocatal Agric Biotechnol 17:196–202. https://doi.org/10.1016/j.bcab.2018.11.022
Mahdinia E, Demirci A, Berenjian A (2019c) Evaluation of vitamin K (menaquinone-7) stability and secretion in glucose and glycerol-based media by Bacillus subtilis natto. Acta Alimentaria, In Press.
Meganathan R (2001) Ubiquinone biosynthesis in microorganisms. FEMS Microbiol Lett 203:131–139. https://doi.org/10.1111/j.1574-6968.2001.tb10831.x
Morikawa M, Kagihiro S, Haruki M, Takano K, Branda S, Kolter R, Kanaya S (2006) Biofilm formation by a Bacillus subtilis strain that produces gamma-polyglutamate. Microbiology 152:2801–2807. https://doi.org/10.1099/mic.0.29060-0
Morishita T, Tamura N, Makino T, Kudo S (1999) Production of menaquinones by lactic acid bacteria. J Dairy Sci 82:1897–1903. https://doi.org/10.3168/jds.S0022-0302(99)75424-X
Pometto AL III, Demirci A (2015) Biofilm in the Food Environment, 2nd edn. John Wiley & Sons, Chicago
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
Qureshi N, Annous BA, Ezeji TC, Karcher P, Maddox IS (2005) Biofilm reactors for industrial bioconversion processes : employing potential of enhanced reaction rates. Microb Cell Factories 24:1–21. https://doi.org/10.1186/1475-2859-4-24
Rahman MS, Ano T, Shoda M (2007) Biofilm fermentation of iturin a by a recombinant strain of Bacillus subtilis 168. J Biotechnol 127:503–507. https://doi.org/10.1016/j.jbiotec.2006.07.013
Ravishankar B, Dound YA, Mehta DS, Ashok BK, de Souza A, Pan MH, Ho CT, Badmaev V and Vaidya AD (2015) Safety assessment of menaquinone-7 for use in human nutrition. J Food Drug Anal 23(1):99 108. https://doi.org/10.1016/j.jfda.2014.03.001
Rishavy MA and Berkner KL (2012) Vitamin K oxygenation, glutamate carboxylation, and processivity: defining the three critical facets of catalysis by the vitamin K–dependent carboxylase. Adv Nutr 3(2):135-148. https://doi.org/10.3945/an.111.001719
Sato T, Yamada Y, Ohtani Y, Mitsui N, Murasawa H, Araki S (2001a) Efficient production of menaquinone (vitamin K2) by a menadione-resistant mutant of Bacillus subtilis. J Ind Microbiol Biotechnol 26:115–120. https://doi.org/10.1038/sj.jim.7000089
Sato T, Yamada Y, Ohtani Y, Mitsui N, Murasawa H, Araki S (2001b) Production of menaquinone (vitamin K2)-7 by Bacillus subtilis. J Biosci Bioeng 91(1):16–20. https://doi.org/10.1016/S1389-1723(01)80104-3
Schurgers LJ, Teunissen KJ, Hamulyák K, Knapen MH, Vik H, Vermeer C (2007) Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood 109:3279–3283. https://doi.org/10.1182/blood-2006-08-040709
Shearer MJ, Newman P (2008) Metabolism and cell biology of vitamin K. Thromb Haemost 100:530–547. https://doi.org/10.1160/TH08-03-0147
Shi J, Zhou S, Kang L, Ling H, Chen J, Duan L, Song Y, Deng Y (2017) Evaluation of the antitumor effects of vitamin K 2 (menaquinone-7) nanoemulsions modified with sialic acid-cholesterol conjugate. Drug Deliv Transl Res 2:1–11. https://doi.org/10.1007/s13346-017-0424-1
Singh R, Puri A, Panda BP (2015) Development of menaquinone-7 enriched nutraceutical: inside into medium engineering and process modeling. J Food Sci Technol 52:5212–5219. https://doi.org/10.1007/s13197-014-1600-7
Song J, Liu H, Wang L, Dai J, Liu Y, Liu H, Zhao G, Wang P, Zheng Z (2014) Enhanced production of vitamin K2 from Bacillus subtilis (natto) by mutation and optimization of the fermentation medium. Braz Arch Biol 57(4):606–612. https://doi.org/10.1590/S1516-8913201402126
Stragier P, Bonamy C, Karmazyn-Campelli C (1988) Processing of a sporulation sigma factor in Bacillus subtilis : how morphological structure could control gene expression. Cell 52:697–704. https://doi.org/10.1016/0092-8674(88)90407-2
Szterk A, Zmysłowski A, Bus K (2018) Identification of cis/trans isomers of menaquinone-7 in food as exemplified by dietary supplements. Food Chem 243:403–409. https://doi.org/10.1016/j.foodchem.2017.10.001
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 67:102–106. https://doi.org/10.1016/0922-338X(89)90188-8
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. https://doi.org/10.1271/bbb.65.2007
Villena GK, Gutiérrez-Correa M (2006) Production of cellulase by Aspergillus niger biofilms developed on polyester cloth. Lett Appl Microbiol 43:262–268. https://doi.org/10.1111/j.1472-765X.2006.01960.x
Vos M, Esposito G, Edirisinghe JN, Vilain S, Haddad DM, Slabbaert JR, Van Meensel S, Schaap O, De Strooper B, Meganathan R, Morais VA (2012) Vitamin K2 is a mitochondrial electron carrier that rescues pink1 deficiency. Science 336(6086):1306–1310. https://doi.org/10.1126/science.1218632
Walther B, Chollet M, (2017) Menaquinones, bacteria, and foods: vitamin K2 in the diet. Vitamin K2- Vital for Health and Wellbeing. Intech, pp 63–82. doi: https://doi.org/10.5772/63712
Walther B, Karl JP, Booth SL, Boyaval P (2013) Menaquinones, bacteria, and the food supply: the relevance of dairy and fermented food products to vitamin K requirements. Adv Nutr 4(4):463–473. https://doi.org/10.3945/an.113.003855
Wang H, Sun X, Wang L, Wu H, Zhao G, Liu H, Wang P, Zheng Z (2018) Coproduction of menaquinone-7 and nattokinase by Bacillus subtilis using soybean curd residue as a renewable substrate combined with a dissolved oxygen control strategy. Ann Microbiol 68(10):655–665. https://doi.org/10.1007/s13213-018-1372-9
Wei H, Zhao G, Liu H, Wang H, Ni W, Wang P, Zheng Z (2018a) A simple and efficient method for the extraction and separation of menaquinone homologs from wet biomass of Flavobacterium. Bioprocess Biosyst Eng 41(1):107–113. https://doi.org/10.1007/s00449-017-1851-6
Wei H, Wang L, Zhao G, Fang Z, Wu H, Wang P, Zheng Z (2018b) Extraction, purification and identification of menaquinones from Flavobacterium meningosepticum fermentation medium. Process Biochem 66:245–253. https://doi.org/10.1016/j.procbio.2018.01.007
Widhalm JR, Ducluzeau AL, Buller NE, Elowsky CG, Olsen LJ, Basset GJ (2012) Phylloquinone (vitamin K1) biosynthesis in plants: two peroxisomal thioesterases of Lactobacillales origin hydrolyze 1,4-dihydroxy-2-naphthoyl-CoA. Plant J 71:205–215. https://doi.org/10.1111/j.1365-313X.2012.04972.x
Wu WJ, Ahn BY (2011) Improved menaquinone (vitamin K2) production in cheonggukjang by optimization of the fermentation conditions. Food Sci Biotechnol 20:1585–1591. https://doi.org/10.1007/s10068-011-0219-y
Xu H, Lee H-Y, Ahn J (2011) Characteristics of biofilm formation by selected foodborne pathogens. J Food Saf 31:91–97. https://doi.org/10.1111/j.1745-4565.2010.00271.x
Xu JZ, Yan WL, Zhang WG (2017) Enhancing menaquinone-7 production in recombinant Bacillus amyloliquefaciens by metabolic pathway engineering. RSC Adv 7(45):28527–28534. https://doi.org/10.1039/c7ra03388e
Yamaguchi M (2006) Regulatory mechanism of food factors in bone metabolism and prevention of osteoporosis. Yakugaku Zasshi 126:1117–1137. https://doi.org/10.1248/yakushi.126.1117
Funding
This work was supported by the USDA National Institute of Food and Agriculture Federal Appropriations under Project PEN04561 and Accession number 1002249.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical statement
This article does not contain any studies with human participants or animals performed by any of the authors.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Mahdinia, E., Demirci, A. & Berenjian, A. Biofilm reactors as a promising method for vitamin K (menaquinone-7) production. Appl Microbiol Biotechnol 103, 5583–5592 (2019). https://doi.org/10.1007/s00253-019-09913-w
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00253-019-09913-w