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A Novel Bi-Functional Fibrinolytic Enzyme with Anticoagulant and Thrombolytic Activities from a Marine-Derived Fungus Aspergillus versicolor ZLH-1

Fibrinolytic enzymes are important components in the treatment of thrombosis-associated disorders. A new bi-functional fibrinolytic enzyme, versiase, was identified from a marine-derived fungus Aspergillus versicolor ZLH-1. The enzyme was isolated from the fungal culture through precipitation with a...

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Autores principales: Zhao, Lihong, Lin, Xiuping, Fu, Jingyun, Zhang, Jun, Tang, Wei, He, Zengguo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9229710/
https://www.ncbi.nlm.nih.gov/pubmed/35736159
http://dx.doi.org/10.3390/md20060356
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author Zhao, Lihong
Lin, Xiuping
Fu, Jingyun
Zhang, Jun
Tang, Wei
He, Zengguo
author_facet Zhao, Lihong
Lin, Xiuping
Fu, Jingyun
Zhang, Jun
Tang, Wei
He, Zengguo
author_sort Zhao, Lihong
collection PubMed
description Fibrinolytic enzymes are important components in the treatment of thrombosis-associated disorders. A new bi-functional fibrinolytic enzyme, versiase, was identified from a marine-derived fungus Aspergillus versicolor ZLH-1. The enzyme was isolated from the fungal culture through precipitation with ammonium sulfate at 90% saturation. Additionally, it was further purified by DEAE-based ion-exchange chromatography, with a recovery of 20.4%. The fibrinolytic enzyme presented as one band on both SDS-PAGE and fibrin-zymogram, with a molecular mass of 37.3 kDa. It was elucidated as a member of metalloprotease in M35 family by proteomic approaches. The homology-modeling analysis revealed that versiase shares significant structural homology wuth the zinc metalloendopeptidase. The enzyme displayed maximum activity at 40 °C and pH 5.0. The activity of versiase was strongly inhibited by the metalloprotease inhibitors EDTA and BGTA. Furthermore, versiase hydrolyzed fibrin directly and indirectly via the activation of plasminogen, and it was able to hydrolyze the three chains (α, β, γ) of fibrin(ogen). Additionally, versiase demonstrated promising thrombolytic and anticoagulant activities, without many side-effects noticed. In conclusion, versiase appears to be a potent fibrinolytic enzyme deserving further investigation.
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spelling pubmed-92297102022-06-25 A Novel Bi-Functional Fibrinolytic Enzyme with Anticoagulant and Thrombolytic Activities from a Marine-Derived Fungus Aspergillus versicolor ZLH-1 Zhao, Lihong Lin, Xiuping Fu, Jingyun Zhang, Jun Tang, Wei He, Zengguo Mar Drugs Article Fibrinolytic enzymes are important components in the treatment of thrombosis-associated disorders. A new bi-functional fibrinolytic enzyme, versiase, was identified from a marine-derived fungus Aspergillus versicolor ZLH-1. The enzyme was isolated from the fungal culture through precipitation with ammonium sulfate at 90% saturation. Additionally, it was further purified by DEAE-based ion-exchange chromatography, with a recovery of 20.4%. The fibrinolytic enzyme presented as one band on both SDS-PAGE and fibrin-zymogram, with a molecular mass of 37.3 kDa. It was elucidated as a member of metalloprotease in M35 family by proteomic approaches. The homology-modeling analysis revealed that versiase shares significant structural homology wuth the zinc metalloendopeptidase. The enzyme displayed maximum activity at 40 °C and pH 5.0. The activity of versiase was strongly inhibited by the metalloprotease inhibitors EDTA and BGTA. Furthermore, versiase hydrolyzed fibrin directly and indirectly via the activation of plasminogen, and it was able to hydrolyze the three chains (α, β, γ) of fibrin(ogen). Additionally, versiase demonstrated promising thrombolytic and anticoagulant activities, without many side-effects noticed. In conclusion, versiase appears to be a potent fibrinolytic enzyme deserving further investigation. MDPI 2022-05-27 /pmc/articles/PMC9229710/ /pubmed/35736159 http://dx.doi.org/10.3390/md20060356 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhao, Lihong
Lin, Xiuping
Fu, Jingyun
Zhang, Jun
Tang, Wei
He, Zengguo
A Novel Bi-Functional Fibrinolytic Enzyme with Anticoagulant and Thrombolytic Activities from a Marine-Derived Fungus Aspergillus versicolor ZLH-1
title A Novel Bi-Functional Fibrinolytic Enzyme with Anticoagulant and Thrombolytic Activities from a Marine-Derived Fungus Aspergillus versicolor ZLH-1
title_full A Novel Bi-Functional Fibrinolytic Enzyme with Anticoagulant and Thrombolytic Activities from a Marine-Derived Fungus Aspergillus versicolor ZLH-1
title_fullStr A Novel Bi-Functional Fibrinolytic Enzyme with Anticoagulant and Thrombolytic Activities from a Marine-Derived Fungus Aspergillus versicolor ZLH-1
title_full_unstemmed A Novel Bi-Functional Fibrinolytic Enzyme with Anticoagulant and Thrombolytic Activities from a Marine-Derived Fungus Aspergillus versicolor ZLH-1
title_short A Novel Bi-Functional Fibrinolytic Enzyme with Anticoagulant and Thrombolytic Activities from a Marine-Derived Fungus Aspergillus versicolor ZLH-1
title_sort novel bi-functional fibrinolytic enzyme with anticoagulant and thrombolytic activities from a marine-derived fungus aspergillus versicolor zlh-1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9229710/
https://www.ncbi.nlm.nih.gov/pubmed/35736159
http://dx.doi.org/10.3390/md20060356
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