Time-dependent catalytic activity in aging condensates

Abstract Biomolecular condensates are dynamic cellular compartments that concentrate proteins and enzymes to regulate biochemical reactions in time and space. While these condensates can enhance enzyme activity, how this function changes as condensates age remains poorly understood. Here, we design...

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Main Authors: Wei Kang, Zhiyue Wu, Xinzhi Huang, Hongbin Qi, Jiaxuan Wu, Jiahui Wang, Jing Li, Sijin Wu, Byung-Ho Kang, Bo Li, Juncai Ma, Chuang Xue
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-62074-5
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author Wei Kang
Zhiyue Wu
Xinzhi Huang
Hongbin Qi
Jiaxuan Wu
Jiahui Wang
Jing Li
Sijin Wu
Byung-Ho Kang
Bo Li
Juncai Ma
Chuang Xue
author_facet Wei Kang
Zhiyue Wu
Xinzhi Huang
Hongbin Qi
Jiaxuan Wu
Jiahui Wang
Jing Li
Sijin Wu
Byung-Ho Kang
Bo Li
Juncai Ma
Chuang Xue
author_sort Wei Kang
collection DOAJ
description Abstract Biomolecular condensates are dynamic cellular compartments that concentrate proteins and enzymes to regulate biochemical reactions in time and space. While these condensates can enhance enzyme activity, how this function changes as condensates age remains poorly understood. Here, we design synthetic catalytic condensates that selectively recruit enzymes to investigate this temporal evolution. We show that catalytic condensates exhibit time-dependent activity: they initially accelerate enzymatic reactions but gradually lose efficiency due to the transition from liquid-like to solid-like states. This aging process, characterized by protein aggregation and loss of selective barriers, impairs enzyme function both in vitro and living cells. We further demonstrate that small molecules which influence aging dynamics can modulate catalytic efficiency of condensates. Our findings show that condensate aging as a key regulator of enzymatic activity and provide crucial insights for designing functional synthetic condensates.
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institution Kabale University
issn 2041-1723
language English
publishDate 2025-07-01
publisher Nature Portfolio
record_format Article
series Nature Communications
spelling doaj-art-39a3d0c95a884c27a3a2b4554e686b1f2025-08-20T04:03:01ZengNature PortfolioNature Communications2041-17232025-07-0116111610.1038/s41467-025-62074-5Time-dependent catalytic activity in aging condensatesWei Kang0Zhiyue Wu1Xinzhi Huang2Hongbin Qi3Jiaxuan Wu4Jiahui Wang5Jing Li6Sijin Wu7Byung-Ho Kang8Bo Li9Juncai Ma10Chuang Xue11MOE Key Laboratory of Bio-Intelligent Manufacturing, State Key Laboratory of Fine Chemicals, Frontiers Science Centre for Smart Materials Oriented Chemical Engineering, School of Bioengineering, Dalian University of TechnologyMOE Key Laboratory of Bio-Intelligent Manufacturing, State Key Laboratory of Fine Chemicals, Frontiers Science Centre for Smart Materials Oriented Chemical Engineering, School of Bioengineering, Dalian University of TechnologyDepartment of Mechanical Engineering, Kennesaw State UniversityMOE Key Laboratory of Bio-Intelligent Manufacturing, State Key Laboratory of Fine Chemicals, Frontiers Science Centre for Smart Materials Oriented Chemical Engineering, School of Bioengineering, Dalian University of TechnologyJiangsu Province Higher Education Key Laboratory of Cell Therapy Nanoformulation, Wisdom Lake Academy of Pharmacy, Xi’an Jiaotong-Liverpool UniversityMOE Key Laboratory of Bio-Intelligent Manufacturing, State Key Laboratory of Fine Chemicals, Frontiers Science Centre for Smart Materials Oriented Chemical Engineering, School of Bioengineering, Dalian University of TechnologySchool of Life Sciences, Centre for Cell & Developmental Biology and State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Shatin, New TerritoriesJiangsu Province Higher Education Key Laboratory of Cell Therapy Nanoformulation, Wisdom Lake Academy of Pharmacy, Xi’an Jiaotong-Liverpool UniversitySchool of Life Sciences, Centre for Cell & Developmental Biology and State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Shatin, New TerritoriesDepartment of Mechanical Engineering, Kennesaw State UniversitySchool of Life Sciences, Centre for Cell & Developmental Biology and State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Shatin, New TerritoriesMOE Key Laboratory of Bio-Intelligent Manufacturing, State Key Laboratory of Fine Chemicals, Frontiers Science Centre for Smart Materials Oriented Chemical Engineering, School of Bioengineering, Dalian University of TechnologyAbstract Biomolecular condensates are dynamic cellular compartments that concentrate proteins and enzymes to regulate biochemical reactions in time and space. While these condensates can enhance enzyme activity, how this function changes as condensates age remains poorly understood. Here, we design synthetic catalytic condensates that selectively recruit enzymes to investigate this temporal evolution. We show that catalytic condensates exhibit time-dependent activity: they initially accelerate enzymatic reactions but gradually lose efficiency due to the transition from liquid-like to solid-like states. This aging process, characterized by protein aggregation and loss of selective barriers, impairs enzyme function both in vitro and living cells. We further demonstrate that small molecules which influence aging dynamics can modulate catalytic efficiency of condensates. Our findings show that condensate aging as a key regulator of enzymatic activity and provide crucial insights for designing functional synthetic condensates.https://doi.org/10.1038/s41467-025-62074-5
spellingShingle Wei Kang
Zhiyue Wu
Xinzhi Huang
Hongbin Qi
Jiaxuan Wu
Jiahui Wang
Jing Li
Sijin Wu
Byung-Ho Kang
Bo Li
Juncai Ma
Chuang Xue
Time-dependent catalytic activity in aging condensates
Nature Communications
title Time-dependent catalytic activity in aging condensates
title_full Time-dependent catalytic activity in aging condensates
title_fullStr Time-dependent catalytic activity in aging condensates
title_full_unstemmed Time-dependent catalytic activity in aging condensates
title_short Time-dependent catalytic activity in aging condensates
title_sort time dependent catalytic activity in aging condensates
url https://doi.org/10.1038/s41467-025-62074-5
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