Enhanced thermostability of nattokinase by rational design of disulfide bond

Abstract Nattokinase, the thrombolytically active substance in the health food natto, nevertheless, its lower thermostability restricts its use in food and pharmaceutical applications. In this study, two heat-resistant variants of nattokinase, designated 50–109 (M1) and 15–271 (M2), were successfull...

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Main Authors: Kongfang Yu, Liangqi Chen, Yaolei Tang, Aixia Ma, Wenhui Zhu, Hong Wang, Xiyu Tang, Yuan Li, Jinyao Li
Format: Article
Language:English
Published: BMC 2025-03-01
Series:Microbial Cell Factories
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Online Access:https://doi.org/10.1186/s12934-025-02681-5
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author Kongfang Yu
Liangqi Chen
Yaolei Tang
Aixia Ma
Wenhui Zhu
Hong Wang
Xiyu Tang
Yuan Li
Jinyao Li
author_facet Kongfang Yu
Liangqi Chen
Yaolei Tang
Aixia Ma
Wenhui Zhu
Hong Wang
Xiyu Tang
Yuan Li
Jinyao Li
author_sort Kongfang Yu
collection DOAJ
description Abstract Nattokinase, the thrombolytically active substance in the health food natto, nevertheless, its lower thermostability restricts its use in food and pharmaceutical applications. In this study, two heat-resistant variants of nattokinase, designated 50–109 (M1) and 15–271 (M2), were successfully obtained by introducing a disulfide bonding strategy. Their half-lives at 55℃ were found to be 2.50-fold and 5.17-fold higher, respectively, than that of the wild type. Furthermore, the specific enzyme activities of the variants, M1 and M2, were also increased by 2.37 and 1.66-fold, respectively. Meanwhile, the combination of two mutants increased the thermostability of nattokinase by 8.0-fold. Bioinformatics analyses indicated that the enhanced thermostability of the M1 and M2 variants was due to the increased rigidity and structural contraction of the overall structure. Finally, the fermentation process of mutant M1 was optimized to increase the expression of nattokinase. Study provides substantial molecular and theoretical support for the industrial production and application of nattokinase.
format Article
id doaj-art-eebc03834ca148b58f77491a0fae6f24
institution DOAJ
issn 1475-2859
language English
publishDate 2025-03-01
publisher BMC
record_format Article
series Microbial Cell Factories
spelling doaj-art-eebc03834ca148b58f77491a0fae6f242025-08-20T02:47:07ZengBMCMicrobial Cell Factories1475-28592025-03-0124111310.1186/s12934-025-02681-5Enhanced thermostability of nattokinase by rational design of disulfide bondKongfang Yu0Liangqi Chen1Yaolei Tang2Aixia Ma3Wenhui Zhu4Hong Wang5Xiyu Tang6Yuan Li7Jinyao Li8Institute of Materia Medica, College of Pharmacy, Xinjiang UniversityInstitute of Materia Medica, College of Pharmacy, Xinjiang UniversityThe Third People’s Hospital of Xinjiang Uygur Autonomous RegionInstitute of Materia Medica, College of Pharmacy, Xinjiang UniversityInstitute of Materia Medica, College of Pharmacy, Xinjiang UniversityInstitute of Materia Medica, College of Pharmacy, Xinjiang UniversityInstitute of Materia Medica, College of Pharmacy, Xinjiang UniversityInstitute of Materia Medica, College of Pharmacy, Xinjiang UniversityInstitute of Materia Medica, College of Pharmacy, Xinjiang UniversityAbstract Nattokinase, the thrombolytically active substance in the health food natto, nevertheless, its lower thermostability restricts its use in food and pharmaceutical applications. In this study, two heat-resistant variants of nattokinase, designated 50–109 (M1) and 15–271 (M2), were successfully obtained by introducing a disulfide bonding strategy. Their half-lives at 55℃ were found to be 2.50-fold and 5.17-fold higher, respectively, than that of the wild type. Furthermore, the specific enzyme activities of the variants, M1 and M2, were also increased by 2.37 and 1.66-fold, respectively. Meanwhile, the combination of two mutants increased the thermostability of nattokinase by 8.0-fold. Bioinformatics analyses indicated that the enhanced thermostability of the M1 and M2 variants was due to the increased rigidity and structural contraction of the overall structure. Finally, the fermentation process of mutant M1 was optimized to increase the expression of nattokinase. Study provides substantial molecular and theoretical support for the industrial production and application of nattokinase.https://doi.org/10.1186/s12934-025-02681-5NattokinaseDisulfide bondEnzyme synthesisThermostabilityBioinformatics design
spellingShingle Kongfang Yu
Liangqi Chen
Yaolei Tang
Aixia Ma
Wenhui Zhu
Hong Wang
Xiyu Tang
Yuan Li
Jinyao Li
Enhanced thermostability of nattokinase by rational design of disulfide bond
Microbial Cell Factories
Nattokinase
Disulfide bond
Enzyme synthesis
Thermostability
Bioinformatics design
title Enhanced thermostability of nattokinase by rational design of disulfide bond
title_full Enhanced thermostability of nattokinase by rational design of disulfide bond
title_fullStr Enhanced thermostability of nattokinase by rational design of disulfide bond
title_full_unstemmed Enhanced thermostability of nattokinase by rational design of disulfide bond
title_short Enhanced thermostability of nattokinase by rational design of disulfide bond
title_sort enhanced thermostability of nattokinase by rational design of disulfide bond
topic Nattokinase
Disulfide bond
Enzyme synthesis
Thermostability
Bioinformatics design
url https://doi.org/10.1186/s12934-025-02681-5
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