Modeling the mechanisms of terpene biosynthesis using deep learning

Field of study: Bioinformatics

Bioactive plant metabolites are an essential source of chemical scaffolds for the development of new medicines. Our group is interested in establishing new cutting-edge methods to harness the biosynthetic potential of plant specialized metabolism for the benefit of human health. One of the most exciting problems in the field is prediction of enzyme activity from its amino acid sequence using computational approaches. In this project, we will assemble a training dataset and design deep learning models for predicting the enzyme substrates, products, and reaction mechanisms directly from the amino acid sequences of terpene synthases. Terpene synthase enzymes are collectively responsible for generating the scaffolds for the largest and the most diverse family of plant specialized metabolites with numerous medical and industrial applications (e.g., paclitaxel or artemisinin).

This PhD project is funded by the European MSCA Doctoral Network ‘ModBioTerp’. The main supervisor is Dr. Tomas Pluskal (IOCB Prague) and co-supervisors are Dr. Christoph Krettler (Enveda Biosciences, USA) and Prof. Aalt-Jan van Dijk (University of Amsterdam, The Netherlands). The monthly stipend includes 2,690 EUR living allowance, 600 EUR mobility allowance, and 660 EUR family allowance (if applicable).

The recruited PhD student must conform to the MSCA Mobility Rule: cannot have resided or carried out his/her main activity (work, studies, etc.) in the Czech Republic for more than 12 months in the 3 years immediately before their recruitment date. Students coming from Czech universities are not eligible for this position.

References:

1. Samusevich R, Hebra T, Bushuiev R, Bushuiev A, Čalounová T, Smrčková H, Chatpatanasiri R, Kulhánek J, Perković M, Engst M, Tajovská A, Sivic J, Pluskal T. Highly accurate discovery of terpene synthases powered by machine learning reveals functional terpene cyclization in Archaea. bioRxiv (2024) https://doi.org/10.1101/2024.01.29.577750
2. Christianson, D. W. Structural and Chemical Biology of Terpenoid Cyclases. Chem. Rev. 117, 11570–11648 (2017) https://doi.org/10.1021/acs.chemrev.7b00287
3. Vattekkatte, A., Garms, S., Brandt, W. & Boland, W. Enhanced structural diversity in terpenoid biosynthesis: enzymes, substrates and cofactors. Org. Biomol. Chem. 16, 348–362 (2018) https://doi.org/10.1039/c7ob02040f