Multifaceted microbial enzyme nattokinase: a comprehensive review on therapeutics applications, production technologies and intellectual property landscape

Cardiovascular diseases (CVDs) have risen drastically after the COVID era as post-COVID symptoms. “Nattokinase” (NK), the thrombolytic enzyme, is known for its substrate-specific thrombolytic, protease, and fibrinolytic activity to ameliorate CVDs. Primarily, NK was isolated from Bacillus subtilis n...

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Main Authors: Tirth Chetankumar Bhatt, Viralkumar B. Mandaliya, Munir Ibrahim, Avani Bhimani, Asmita Detroja, Jaykumar Koradiya, Gaurav Sanghvi, Ashok Kumar Bishoyi
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Current Research in Biotechnology
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590262825000474
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author Tirth Chetankumar Bhatt
Viralkumar B. Mandaliya
Munir Ibrahim
Avani Bhimani
Asmita Detroja
Jaykumar Koradiya
Gaurav Sanghvi
Ashok Kumar Bishoyi
author_facet Tirth Chetankumar Bhatt
Viralkumar B. Mandaliya
Munir Ibrahim
Avani Bhimani
Asmita Detroja
Jaykumar Koradiya
Gaurav Sanghvi
Ashok Kumar Bishoyi
author_sort Tirth Chetankumar Bhatt
collection DOAJ
description Cardiovascular diseases (CVDs) have risen drastically after the COVID era as post-COVID symptoms. “Nattokinase” (NK), the thrombolytic enzyme, is known for its substrate-specific thrombolytic, protease, and fibrinolytic activity to ameliorate CVDs. Primarily, NK was isolated from Bacillus subtilis natto using either solid- or liquid-state fermentation technology. Later, the researchers studied the arpN gene, which encodes NK and is used in various biotechnological approaches with different hosts such as Bacillus spp., Escherichia coli, Lactobacillus spp., and Pichia pastoris. The global market potential of NK in treating CVDs has recently garnered attention, leading to a demand for bulk production and ultrapure forms of NK. This demand has put pressure on strain improvements and innovation in production technology. The patent scenario suggested that NK have been given more attention with 763 patents compared to streptokinase, staphylokinase and serratiopeptidase. This review critically examined the biotechnological aspects of NK in amelioration of CVDs, focusing on current production technologies, strain improvement strategies, protected NK innovations, and future research directions. It emphasizes the need for advanced approaches like CRISPR technology and novel production protocols to develop high-quality, ultrapure NK. It is also aligning with Sustainable Development Goal (SDG) 3: “Good Health and Well-Being.”
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spelling doaj-art-d1a83fb68f3e44db94ad6e746a93db8f2025-07-19T04:39:14ZengElsevierCurrent Research in Biotechnology2590-26282025-01-0110100316Multifaceted microbial enzyme nattokinase: a comprehensive review on therapeutics applications, production technologies and intellectual property landscapeTirth Chetankumar Bhatt0Viralkumar B. Mandaliya1Munir Ibrahim2Avani Bhimani3Asmita Detroja4Jaykumar Koradiya5Gaurav Sanghvi6Ashok Kumar Bishoyi7Department of Microbiology, Faculty of Science, Marwadi University, Rajkot, Gujarat, IndiaDepartment of Microbiology, Faculty of Science, Marwadi University, Rajkot, Gujarat, IndiaDepartment of Microbiology, Faculty of Science, Marwadi University, Rajkot, Gujarat, IndiaDepartment of Microbiology, Faculty of Science, Marwadi University, Rajkot, Gujarat, IndiaDepartment of Microbiology, Faculty of Science, Marwadi University, Rajkot, Gujarat, IndiaDepartment of Microbiology, Faculty of Science, Marwadi University, Rajkot, Gujarat, IndiaDepartment of Microbiology, Faculty of Science, Marwadi University, Rajkot, Gujarat, IndiaDepartment of Microbiology, Faculty of Science, Marwadi University, Rajkot, Gujarat, India; Corresponding author.Cardiovascular diseases (CVDs) have risen drastically after the COVID era as post-COVID symptoms. “Nattokinase” (NK), the thrombolytic enzyme, is known for its substrate-specific thrombolytic, protease, and fibrinolytic activity to ameliorate CVDs. Primarily, NK was isolated from Bacillus subtilis natto using either solid- or liquid-state fermentation technology. Later, the researchers studied the arpN gene, which encodes NK and is used in various biotechnological approaches with different hosts such as Bacillus spp., Escherichia coli, Lactobacillus spp., and Pichia pastoris. The global market potential of NK in treating CVDs has recently garnered attention, leading to a demand for bulk production and ultrapure forms of NK. This demand has put pressure on strain improvements and innovation in production technology. The patent scenario suggested that NK have been given more attention with 763 patents compared to streptokinase, staphylokinase and serratiopeptidase. This review critically examined the biotechnological aspects of NK in amelioration of CVDs, focusing on current production technologies, strain improvement strategies, protected NK innovations, and future research directions. It emphasizes the need for advanced approaches like CRISPR technology and novel production protocols to develop high-quality, ultrapure NK. It is also aligning with Sustainable Development Goal (SDG) 3: “Good Health and Well-Being.”http://www.sciencedirect.com/science/article/pii/S2590262825000474Clinical trialsFermentation technologyNattokinasePatent landscapePurification methods
spellingShingle Tirth Chetankumar Bhatt
Viralkumar B. Mandaliya
Munir Ibrahim
Avani Bhimani
Asmita Detroja
Jaykumar Koradiya
Gaurav Sanghvi
Ashok Kumar Bishoyi
Multifaceted microbial enzyme nattokinase: a comprehensive review on therapeutics applications, production technologies and intellectual property landscape
Current Research in Biotechnology
Clinical trials
Fermentation technology
Nattokinase
Patent landscape
Purification methods
title Multifaceted microbial enzyme nattokinase: a comprehensive review on therapeutics applications, production technologies and intellectual property landscape
title_full Multifaceted microbial enzyme nattokinase: a comprehensive review on therapeutics applications, production technologies and intellectual property landscape
title_fullStr Multifaceted microbial enzyme nattokinase: a comprehensive review on therapeutics applications, production technologies and intellectual property landscape
title_full_unstemmed Multifaceted microbial enzyme nattokinase: a comprehensive review on therapeutics applications, production technologies and intellectual property landscape
title_short Multifaceted microbial enzyme nattokinase: a comprehensive review on therapeutics applications, production technologies and intellectual property landscape
title_sort multifaceted microbial enzyme nattokinase a comprehensive review on therapeutics applications production technologies and intellectual property landscape
topic Clinical trials
Fermentation technology
Nattokinase
Patent landscape
Purification methods
url http://www.sciencedirect.com/science/article/pii/S2590262825000474
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