Enzyme catalysis as a tool in building block synthesis
Time: Fri 2025-09-26 10.00
Location: F3 (Flodis), Lindstedtsvägen 26 & 28, Stockholm
Video link: https://kth-se.zoom.us/j/65349554799
Language: English
Subject area: Chemistry
Doctoral student: Elisabeth Söderberg , Ytbehandlingsteknik, Science for Life Laboratory, SciLifeLab, Per-Olof Syrén
Opponent: Associate Professor Mélanie Hall, University of Graz, Graz, Austria
Supervisor: Associate professor Per-Olof Syrén, Ytbehandlingsteknik, Science for Life Laboratory, SciLifeLab
QC 20250829
Abstract
Traditional production of chemicals often relies on the use of petroleum-based or toxic raw materials, harsh conditions, and suffers from inefficient reactions. Hence, improvements are needed to sustainably produce chemicals. Enzymes, nature’s catalysts, are a potential solution to some of these issues. They increase the rate of reactions under mild conditions with high substrate specificity. However, they often need to be modified to work in industrial settings. Efforts also need to be made to avoid toxic raw materials and the production of harmful products. This thesis aims to develop more sustainable methods for chemical synthesis by employing enzyme catalysis in an interdisciplinary approach. In paper I, chemoenzymatic methods were developed for the valorization and polymerization of a terpene by-product from the paper and pulp industry to create biobased plastics. Paper II explored biocatalytic amide bond formation. Robust ancestral enzymes with altered activities were designed using ancestral sequence reconstruction, a technique leveraging evolutionary information to predict ancestral protein sequences. The extant enzyme and the ancestral variants were used in the coupling of a set of safe substrates derived from an in silico toxicity filtering pipeline. Paper III investigated observed differences between the extant enzyme and one ancestor from paper II. Through computational simulations and enzyme mutant testing, plausible key residues responsible for the change were identified. A highly active ancestral mutant also demonstrated successful scaled-up synthesis with cofactor recycling. Lastly, in paper IV, ecotoxicity prediction models were applied to the substrate dataset from paper II. The predictions had low reliability, and ways to improve the reliability of ecotoxicity predictions were discussed. In summary, this thesis highlights alternative routes for more sustainable chemical synthesis and the potential of enzyme catalysis.