preprint · bioRxiv (Cold Spring Harbor Laboratory) · 2024

Structure-enabled enzyme function prediction unveils elusive terpenoid biosynthesis in archaea

Raman Samusevich, Téo Hebra, Roman Bushuiev, Martin Engst, Jonáš Kulhánek, Anton Bushuiev, Joshua D. Smith, Tereza Čalounová, Helena Smrčková, Marina Molineris, Renana Schwartz, Adéla Tajovská, Milana Perković, Ratthachat Chatpatanasiri, Sotirios C. Kampranis, Dan Thomas Major, Josef Šivic, Tomáš Pluskal

Cited by 9Open access

Abstract

Abstract The exponential growth of uncharacterized enzyme sequences in genomic repositories demands novel tools for functional annotation. Here, we combined alignment-driven structural domain analysis with protein language models to create EnzymeExplorer, a machine-learning pipeline for enzyme function prediction. We applied this approach to terpene synthases, which present an ideal model case because they catalyze complex carbocationic rearrangements whose product outcomes cannot be predicted from active site residues alone. We detected new structural domains and achieved state-of-the-art performance on function prediction. By analyzing the UniRef90 database, we identified terpene synthases overlooked by current computational methods. Remarkably, we uncovered and experimentally validated the widespread biosynthesis of terpenoids in archaea. Our approach offers a powerful framework for characterizing enzyme “dark matter” in the rapidly expanding genomic and metagenomic datasets.

Cite this paper

APA 7

Samusevich, R., Hebra, T., Bushuiev, R., Engst, M., Kulhánek, J., Bushuiev, A., Smith, J. D., Čalounová, T., Smrčková, H., Molineris, M., Schwartz, R., Tajovská, A., Perković, M., Chatpatanasiri, R., Kampranis, S. C., Major, D. T., Šivic, J., & Pluskal, T. (2024). Structure-enabled enzyme function prediction unveils elusive terpenoid biosynthesis in archaea. bioRxiv (Cold Spring Harbor Laboratory). https://doi.org/10.1101/2024.01.29.577750

MLA 9

Samusevich, Raman, et al. “Structure-enabled enzyme function prediction unveils elusive terpenoid biosynthesis in archaea.” bioRxiv (Cold Spring Harbor Laboratory), 2024, https://doi.org/10.1101/2024.01.29.577750.

Chicago

Samusevich, Raman, Téo Hebra, Roman Bushuiev, Martin Engst, Jonáš Kulhánek, Anton Bushuiev, Joshua D. Smith, et al. 2024. “Structure-enabled enzyme function prediction unveils elusive terpenoid biosynthesis in archaea.” bioRxiv (Cold Spring Harbor Laboratory). https://doi.org/10.1101/2024.01.29.577750.

Harvard

Samusevich, R. et al. (2024) ‘Structure-enabled enzyme function prediction unveils elusive terpenoid biosynthesis in archaea’, bioRxiv (Cold Spring Harbor Laboratory). Available at: https://doi.org/10.1101/2024.01.29.577750.

BibTeX

@misc{samusevich2024structure,
  title = {{Structure-enabled enzyme function prediction unveils elusive terpenoid biosynthesis in archaea}},
  author = {Samusevich, Raman and Hebra, Téo and Bushuiev, Roman and Engst, Martin and Kulhánek, Jonáš and Bushuiev, Anton and Smith, Joshua D. and Čalounová, Tereza and Smrčková, Helena and Molineris, Marina and Schwartz, Renana and Tajovská, Adéla and Perković, Milana and Chatpatanasiri, Ratthachat and Kampranis, Sotirios C. and Major, Dan Thomas and Šivic, Josef and Pluskal, Tomáš},
  journal = {bioRxiv (Cold Spring Harbor Laboratory)},
  year = {2024},
  doi = {10.1101/2024.01.29.577750}
}

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