Structure‐Guided Engineering of a Versatile Urethanase Improves Its Polyurethane Depolymerization Activity

Bibliographic Details
Title: Structure‐Guided Engineering of a Versatile Urethanase Improves Its Polyurethane Depolymerization Activity
Authors: Zhishuai Li, Xu Han, Lin Cong, Parinita Singh, Pedro Paiva, Yannick Branson, Wenshuo Li, Yangyang Chen, Da'san M. M. Jaradat, Frank Lennartz, Thomas Bayer, Louis Schmidt, Ulrike Garscha, Song You, Pedro Alexandrino Fernandes, Maria João Ramos, Uwe T. Bornscheuer, Gert Weber, Ren Wei, Weidong Liu
Source: Advanced Science, Vol 12, Iss 13, Pp n/a-n/a (2025)
Publisher Information: Wiley, 2025.
Publication Year: 2025
Collection: LCC:Science
Subject Terms: crystal structures, enzyme engineering, molecular dynamics simulations, plastic degradation, polyurethane, urethanase, Science
More Details: Abstract Polyurethane (PUR), the fifth most prevalent synthetic polymer, substantially contributes to the global plastic waste problem. Biotechnology‐based recycling methods have recently emerged as innovative solutions to plastic waste disposal and sparked interest among scientific communities and industrial stakeholders in discovering and designing highly active plastic‐degrading enzymes. Here, the ligand‐free crystal structure of UMG‐SP2, a metagenome‐derived urethanase with depolymerization activities, at 2.59 Å resolution, as well as its (co‐)structures bound to a suicide hydrolase inhibitor and a short‐chain carbamate substrate at 2.16 and 2.40 Å resolutions, respectively, is reported. Structural analysis and molecular dynamics simulations reveal that the flexible loop L3 consisting of residues 219–226 is crucial for regulating the hydrolytic activity of UMG‐SP2. The semi‐rational redesign of UMG‐SP2 reveals superior variants, A141G and Q399A, exhibiting over 30.7‐ and 7.4‐fold increased activities on polyester‐PUR and a methylene diamine derivative of PUR, respectively, compared to the wild‐type enzyme. These findings advance the understanding of the structure–function relationship of PUR‐hydrolyzing enzymes, which hold great promise for developing effective industrial PUR recycling processes and mitigating the environmental footprint of plastic waste.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2198-3844
Relation: https://doaj.org/toc/2198-3844
DOI: 10.1002/advs.202416019
Access URL: https://doaj.org/article/d29e2f19107c4e6a83bd56c1c0d2bd9c
Accession Number: edsdoj.29e2f19107c4e6a83bd56c1c0d2bd9c
Database: Directory of Open Access Journals
More Details
ISSN:21983844
DOI:10.1002/advs.202416019
Published in:Advanced Science
Language:English