nattokinase

{{Short description|Enzyme commonly found in natto}}

{{Infobox nonhuman protein

| Name = Subtilisin NAT

| Symbol = aprN

| image = File:4dwwnattokinase.png

| UniProt = P35835

| Organism = Bacillus subtilis natto

| ECnumber = 3.4.21.62

| caption = Crystal structure of nattokinase. PDB {{PDBe|4dww}}.{{cite journal | vauthors = Yanagisawa Y, Chatake T, Chiba-Kamoshida K, Naito S, Ohsugi T, Sumi H, Yasuda I, Morimoto Y | display-authors = 6 | title = Purification, crystallization and preliminary X-ray diffraction experiment of nattokinase from Bacillus subtilis natto | journal = Acta Crystallographica. Section F, Structural Biology and Crystallization Communications | volume = 66 | issue = Pt 12 | pages = 1670–73 | date = December 2010 | pmid = 21139221 | pmc = 2998380 | doi = 10.1107/S1744309110043137 }}

}}

Nattokinase (pronounced {{respell|nuh|TOH|kin|ayss}}) is an enzyme extracted and purified from a Japanese food called nattō. Nattō is produced by fermentation by adding the bacterium Bacillus subtilis var natto, which also produces the enzyme, to boiled soybeans. While other soy foods contain enzymes, it is only the nattō preparation that contains the specific nattokinase enzyme under the Japan Nattokinase Administration and Ministry of Health, Labour and Welfare.

In spite of its name, nattokinase is not a kinase enzyme (and should not be pronounced as such), but a serine protease of the subtilisin family (99.5% identical with aprE). Rather, it is named for the fact that it is an enzyme produced by nattōkin ({{langx|ja|納豆 菌}})(納豆 菌), the Japanese name for Bacillus subtilis var natto. When in contact with human blood or blood clots, it exhibits a strong fibrinolytic activity and works by inactivating plasminogen activator inhibitor 1 (PAI-1).{{cite journal | vauthors = Urano T, Ihara H, Umemura K, Suzuki Y, Oike M, Akita S, Tsukamoto Y, Suzuki I, Takada A | display-authors = 6 | title = The profibrinolytic enzyme subtilisin NAT purified from Bacillus subtilis Cleaves and inactivates plasminogen activator inhibitor type 1 | journal = The Journal of Biological Chemistry | volume = 276 | issue = 27 | pages = 24690–96 | date = July 2001 | pmid = 11325965 | doi = 10.1074/jbc.M101751200 | doi-access = free }}{{cite journal | vauthors = Fujita M, Nomura K, Hong K, Ito Y, Asada A, Nishimuro S | title = Purification and characterization of a strong fibrinolytic enzyme (nattokinase) in the vegetable cheese natto, a popular soybean fermented food in Japan | journal = Biochemical and Biophysical Research Communications | volume = 197 | issue = 3 | pages = 1340–47 | date = December 1993 | pmid = 8280151 | doi = 10.1006/bbrc.1993.2624 }}{{Cite web|url=https://www.pharmacistanswers.com/questions/can-you-take-nattokinase-with-coumadin-warfarin|title=Can You Take Nattokinase With Coumadin (Warfarin)?|website=PharmacistAnswers|language=en|access-date=2019-02-20}}{{cite journal | vauthors = Sumi H, Hamada H, Tsushima H, Mihara H, Muraki H | title = A novel fibrinolytic enzyme (nattokinase) in the vegetable cheese Natto; a typical and popular soybean food in the Japanese diet | journal = Experientia | volume = 43 | issue = 10 | pages = 1110–11 | date = October 1987 | pmid = 3478223 | doi = 10.1007/bf01956052 | s2cid = 13476341 }} Although it should be expected to be digested and inactivated in the human gut like other proteins, one group reported that nattokinase has some effect even when taken orally and consumed.{{cite journal | vauthors = Chen H, McGowan EM, Ren N, Lal S, Nassif N, Shad-Kaneez F, Qu X, Lin Y | display-authors = 6 | title = Nattokinase: A Promising Alternative in Prevention and Treatment of Cardiovascular Diseases | journal = Biomarker Insights | volume = 13 | date = 2018 | pmid = 30013308 | doi = 10.1177/1177271918785130 | pmc = 6043915 | doi-access = free }}

Nattokinase can also be sold as a dietary supplement. It can now be produced by recombinant means{{cite journal | vauthors = Liang X, Jia S, Sun Y, Chen M, Chen X, Zhong J, Huan L | title = Secretory expression of nattokinase from Bacillus subtilis YF38 in Escherichia coli | journal = Molecular Biotechnology | volume = 37 | issue = 3 | pages = 187–94 | date = November 2007 | pmid = 17952663 | doi = 10.1007/s12033-007-0060-y | s2cid = 11595829 }}{{cite journal | vauthors = Li X, Wang X, Xiong S, Zhang J, Cai L, Yang Y | title = Expression and purification of recombinant nattokinase in Spodoptera frugiperda cells | journal = Biotechnology Letters | volume = 29 | issue = 10 | pages = 1459–64 | date = October 2007 | pmid = 17581705 | doi = 10.1007/s10529-007-9426-2 | s2cid = 26608552 }} and in batch culture,{{cite journal | vauthors = Cho YH, Song JY, Kim KM, Kim MK, Lee IY, Kim SB, Kim HS, Han NS, Lee BH, Kim BS | display-authors = 6 | title = Production of nattokinase by batch and fed-batch culture of Bacillus subtilis | journal = New Biotechnology | volume = 27 | issue = 4 | pages = 341–46 | date = September 2010 | pmid = 20541632 | doi = 10.1016/j.nbt.2010.06.003 }}{{cite journal | vauthors = Kwon EY, Kim KM, Kim MK, Lee IY, Kim BS | title = Production of nattokinase by high cell density fed-batch culture of Bacillus subtilis | journal = Bioprocess and Biosystems Engineering | volume = 34 | issue = 7 | pages = 789–93 | date = September 2011 | pmid = 21336955 | doi = 10.1007/s00449-011-0527-x | s2cid = 38816306 }} rather than relying on extraction from nattō or eating it whole.