An aggregation-induced conformation locking strategy facilitates the activation of lipase biocatalyst

Abstract Lipase represents one of the most important industrial biocatalysts, with a global market value of $590.5 million by 2020. However, their catalytic efficiency is often hindered by a closed “lid” conformation. Here, we present an aggregation-induced conformation locking strategy that enables...

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Main Authors: Anlian Huang, Zhi-Wei Li, Lihong Guo, Ningyi Zhong, Linjing Tong, Yanbin Xu, Xiaomin Ma, Fang Zhu, Guosheng Chen, Siming Huang, Gangfeng Ouyang
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-59824-w
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author Anlian Huang
Zhi-Wei Li
Lihong Guo
Ningyi Zhong
Linjing Tong
Yanbin Xu
Xiaomin Ma
Fang Zhu
Guosheng Chen
Siming Huang
Gangfeng Ouyang
author_facet Anlian Huang
Zhi-Wei Li
Lihong Guo
Ningyi Zhong
Linjing Tong
Yanbin Xu
Xiaomin Ma
Fang Zhu
Guosheng Chen
Siming Huang
Gangfeng Ouyang
author_sort Anlian Huang
collection DOAJ
description Abstract Lipase represents one of the most important industrial biocatalysts, with a global market value of $590.5 million by 2020. However, their catalytic efficiency is often hindered by a closed “lid” conformation. Here, we present an aggregation-induced conformation locking strategy that enables the facile synthesis of highly activated lipase hybrid biocatalysts. Lipase is self-activated into an open-lid conformation via solvent-mediated aggregation, followed by conformational locking within a two-dimensional metal-organic framework (MOF). The resulting MOF biocatalyst provides high accessibility to the locked lipase aggregates through its long-range ordered pore channels, achieving a hydrolytic efficiency 5.30 times greater than that of native lipase. To the best of our knowledge, this represents a record-high activation efficiency for ester hydrolysis among the reported lipase-based hybrid biocatalysts to date. We also demonstrate its feasibility to catalytically accelerate transesterification and esterification reactions, showing up to as 6.64 times higher yield than native lipase and impressive recyclability.
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spelling doaj-art-67bfcb835ab54042a04a4d07b455c2ec2025-08-20T01:53:23ZengNature PortfolioNature Communications2041-17232025-05-0116111310.1038/s41467-025-59824-wAn aggregation-induced conformation locking strategy facilitates the activation of lipase biocatalystAnlian Huang0Zhi-Wei Li1Lihong Guo2Ningyi Zhong3Linjing Tong4Yanbin Xu5Xiaomin Ma6Fang Zhu7Guosheng Chen8Siming Huang9Gangfeng Ouyang10MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-sen UniversityMOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-sen UniversityMOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-sen UniversityMOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-sen UniversityMOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-sen UniversityGuangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical UniversityShenzhen Medical Academy of Research and TranslationMOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-sen UniversityMOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-sen UniversityGuangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical UniversityMOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-sen UniversityAbstract Lipase represents one of the most important industrial biocatalysts, with a global market value of $590.5 million by 2020. However, their catalytic efficiency is often hindered by a closed “lid” conformation. Here, we present an aggregation-induced conformation locking strategy that enables the facile synthesis of highly activated lipase hybrid biocatalysts. Lipase is self-activated into an open-lid conformation via solvent-mediated aggregation, followed by conformational locking within a two-dimensional metal-organic framework (MOF). The resulting MOF biocatalyst provides high accessibility to the locked lipase aggregates through its long-range ordered pore channels, achieving a hydrolytic efficiency 5.30 times greater than that of native lipase. To the best of our knowledge, this represents a record-high activation efficiency for ester hydrolysis among the reported lipase-based hybrid biocatalysts to date. We also demonstrate its feasibility to catalytically accelerate transesterification and esterification reactions, showing up to as 6.64 times higher yield than native lipase and impressive recyclability.https://doi.org/10.1038/s41467-025-59824-w
spellingShingle Anlian Huang
Zhi-Wei Li
Lihong Guo
Ningyi Zhong
Linjing Tong
Yanbin Xu
Xiaomin Ma
Fang Zhu
Guosheng Chen
Siming Huang
Gangfeng Ouyang
An aggregation-induced conformation locking strategy facilitates the activation of lipase biocatalyst
Nature Communications
title An aggregation-induced conformation locking strategy facilitates the activation of lipase biocatalyst
title_full An aggregation-induced conformation locking strategy facilitates the activation of lipase biocatalyst
title_fullStr An aggregation-induced conformation locking strategy facilitates the activation of lipase biocatalyst
title_full_unstemmed An aggregation-induced conformation locking strategy facilitates the activation of lipase biocatalyst
title_short An aggregation-induced conformation locking strategy facilitates the activation of lipase biocatalyst
title_sort aggregation induced conformation locking strategy facilitates the activation of lipase biocatalyst
url https://doi.org/10.1038/s41467-025-59824-w
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