Enzymatic cleavage of model lignin dimers depends on pH, enzyme, and bond type

Abstract Lignin is composed of phenylpropanoid monomers linked by ether and carbon-carbon bonds to form a complex heterogeneous structure. Bond-specific studies of lignin-modifying enzymes (LMEs; e.g., laccases and peroxidases) are limited by the polymerization of model lignin substrates and repolym...

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Main Authors: Jenny R. Onley, Kshitiz Gupta, Markus de Raad, Benjamin P. Bowen, Stephen Tan, Sam Yoder, Kenneth L. Sale, Anup K. Singh, Blake A. Simmons, Paul D. Adams, Trent R. Northen, Kai Deng
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-88571-7
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author Jenny R. Onley
Kshitiz Gupta
Markus de Raad
Benjamin P. Bowen
Stephen Tan
Sam Yoder
Kenneth L. Sale
Anup K. Singh
Blake A. Simmons
Paul D. Adams
Trent R. Northen
Kai Deng
author_facet Jenny R. Onley
Kshitiz Gupta
Markus de Raad
Benjamin P. Bowen
Stephen Tan
Sam Yoder
Kenneth L. Sale
Anup K. Singh
Blake A. Simmons
Paul D. Adams
Trent R. Northen
Kai Deng
author_sort Jenny R. Onley
collection DOAJ
description Abstract Lignin is composed of phenylpropanoid monomers linked by ether and carbon-carbon bonds to form a complex heterogeneous structure. Bond-specific studies of lignin-modifying enzymes (LMEs; e.g., laccases and peroxidases) are limited by the polymerization of model lignin substrates and repolymerization of cleavage products. Here we present a high throughput platform to screen LME activities on four tagged model lignin compounds that represent the β-O-4’, β-β’, 5–5’, and 4-O-5’ linkages in lignin. We utilized nanostructure-initiator mass spectrometry (NIMS) and model lignin compounds with tags containing perfluorinated and cationic moieties, which effectively limit polymerization and condensation of the substrates and their degrading products. Sub-microliter sample droplets were printed on the NIMS chip with a novel robotics method. This rapid platform enabled characterization of LMEs across a range of pH 3–10 and relative quantification of modified (typically oxidized), cleaved, and polymerized products. All tested enzymes oxidized the four substrates and cleaved the β-O-4’ and β-β’ substrates to monomeric products. We discovered that the active pH range depended on both the substrate and the enzyme type. This has important applications for biomass conversion to biofuels and bioproducts, where the relative percentages of different bond types in lignin varies depending on feedstock and chemical pretreatment methods.
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spelling doaj-art-80e663d7ee62490591a925d8f4e34f0b2025-08-20T03:48:06ZengNature PortfolioScientific Reports2045-23222025-03-0115111110.1038/s41598-025-88571-7Enzymatic cleavage of model lignin dimers depends on pH, enzyme, and bond typeJenny R. Onley0Kshitiz Gupta1Markus de Raad2Benjamin P. Bowen3Stephen Tan4Sam Yoder5Kenneth L. Sale6Anup K. Singh7Blake A. Simmons8Paul D. Adams9Trent R. Northen10Kai Deng11Technology Division, Joint BioEnergy InstituteTechnology Division, Joint BioEnergy InstituteEnvironmental Genomics and Systems Biology Division, Lawrence Berkeley National LaboratoryEnvironmental Genomics and Systems Biology Division, Lawrence Berkeley National LaboratoryTechnology Division, Joint BioEnergy InstituteTechnology Division, Joint BioEnergy InstituteBiosecurity and Bioassurance Department, Sandia National LaboratoriesTechnology Division, Joint BioEnergy InstituteBiological Systems and Engineering Division, Lawrence Berkeley National LaboratoryTechnology Division, Joint BioEnergy InstituteTechnology Division, Joint BioEnergy InstituteTechnology Division, Joint BioEnergy InstituteAbstract Lignin is composed of phenylpropanoid monomers linked by ether and carbon-carbon bonds to form a complex heterogeneous structure. Bond-specific studies of lignin-modifying enzymes (LMEs; e.g., laccases and peroxidases) are limited by the polymerization of model lignin substrates and repolymerization of cleavage products. Here we present a high throughput platform to screen LME activities on four tagged model lignin compounds that represent the β-O-4’, β-β’, 5–5’, and 4-O-5’ linkages in lignin. We utilized nanostructure-initiator mass spectrometry (NIMS) and model lignin compounds with tags containing perfluorinated and cationic moieties, which effectively limit polymerization and condensation of the substrates and their degrading products. Sub-microliter sample droplets were printed on the NIMS chip with a novel robotics method. This rapid platform enabled characterization of LMEs across a range of pH 3–10 and relative quantification of modified (typically oxidized), cleaved, and polymerized products. All tested enzymes oxidized the four substrates and cleaved the β-O-4’ and β-β’ substrates to monomeric products. We discovered that the active pH range depended on both the substrate and the enzyme type. This has important applications for biomass conversion to biofuels and bioproducts, where the relative percentages of different bond types in lignin varies depending on feedstock and chemical pretreatment methods.https://doi.org/10.1038/s41598-025-88571-7LigninLaccasePeroxidaseMass spectrometry
spellingShingle Jenny R. Onley
Kshitiz Gupta
Markus de Raad
Benjamin P. Bowen
Stephen Tan
Sam Yoder
Kenneth L. Sale
Anup K. Singh
Blake A. Simmons
Paul D. Adams
Trent R. Northen
Kai Deng
Enzymatic cleavage of model lignin dimers depends on pH, enzyme, and bond type
Scientific Reports
Lignin
Laccase
Peroxidase
Mass spectrometry
title Enzymatic cleavage of model lignin dimers depends on pH, enzyme, and bond type
title_full Enzymatic cleavage of model lignin dimers depends on pH, enzyme, and bond type
title_fullStr Enzymatic cleavage of model lignin dimers depends on pH, enzyme, and bond type
title_full_unstemmed Enzymatic cleavage of model lignin dimers depends on pH, enzyme, and bond type
title_short Enzymatic cleavage of model lignin dimers depends on pH, enzyme, and bond type
title_sort enzymatic cleavage of model lignin dimers depends on ph enzyme and bond type
topic Lignin
Laccase
Peroxidase
Mass spectrometry
url https://doi.org/10.1038/s41598-025-88571-7
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