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Cited by 9Biofuel production and bioconversionFungal and yeast genetics researchEnzyme Production and Characterization

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A seven-transmembrane methyltransferase catalysing N-terminal histidine methylation of lytic polysaccharide monooxygenases

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Batth, Tanveer S., Simonsen, Jonas L., Hernández-Rollán, Cristina, Brander, Søren, Morth, Jens Preben, Johansen, Katja S., Nørholm, Morten H. H., Hoof, Jakob B., Olsen, Jesper V.·2023·Nature Communications
DOI 10.1038/s41467-023-39875-7PMC PMC10349129

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Abstract

Lytic polysaccharide monooxygenases (LPMOs) are oxidative enzymes that help break down lignocellulose, making them highly attractive for improving biomass utilization in industrial biotechnology. The catalytically essential N-terminal histidine (His1) of LPMOs is post-translationally modified by methylation in filamentous fungi to protect them from auto-oxidative inactivation, however, the responsible methyltransferase enzyme is unknown. Using mass-spectrometry-based quantitative proteomics in combination with systematic CRISPR/Cas9 knockout screening in Aspergillus nidulans , we identify the N-terminal histidine methyltransferase (NHMT) encoded by the gene AN4663. Targeted proteomics confirm that NHMT was solely responsible for His1 methylation of LPMOs. NHMT is predicted to encode a unique seven-transmembrane segment anchoring a soluble methyltransferase domain. Co-localization studies show endoplasmic reticulum residence of NHMT and co-expression in the industrial production yeast Komagataella phaffii with LPMOs results in His1 methylation of the LPMOs. This demonstrates the biotechnological potential of recombinant production of proteins and peptides harbouring this specific post-translational modification.

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Metadata

Authors
Batth, T. S., Simonsen, J. L., Hernández-Rollán, C., Brander, S., Morth, J. P., Johansen, K. S., Nørholm, M. H. H., Hoof, J. B., & Olsen, J. V.
Affiliations
  • University of Copenhagen (DK)
  • Technical University of Denmark (DK)
  • Novo Nordisk Foundation (DK)
Corresponding author
Batth, Tanveer S.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2023-07-14
Volume
14
Issue
1
Pages
4202-4202
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-023-39875-7
PMC
PMC10349129
OpenAlex
W4384339461
Cited by
9
References
1
Citations by year
2026: 3 · 2025: 4 · 2024: 1 · 2023: 1
FWCI
0.71
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Technical University of Denmark, DTU Orbit (Technical University of Denmark, DTU) (submittedVersion, cc-by)
Funders
Novo Nordisk Fonden (NNF14CC0001, NNF17SA0027704)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › Biofuel production and bioconversion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Enzyme Production and Characterization
Keywords
lytic polysaccharide monooxygenase, methyltransferase, seven-transmembrane proteins, post-translational modification, Aspergillus nidulans, endoplasmic reticulum, lignocellulose degradation, Pichia pastoris, filamentous fungi, CRISPR/Cas9 knockout screening
MeSH terms
Histidine, Mixed Function Oxygenases, Methylation, Methyltransferases, Polysaccharides, Protein Processing, Post-Translational

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