Silvia Osuna (UdG) — Exploring the enantioconvergent polycyclization of linear terpenoids catalyzed by Squalene Hopene Cyclase

exploring-the-enantioconvergent-polycyclization-of-linear-terpenoids-catalyzed-by-squalene-hopene-cyclase

Silvia Osuna (UdG) — Exploring the enantioconvergent polycyclization of linear terpenoids catalyzed by Squalene Hopene Cyclase

/ Mon, 05/26/2025 - 15:46
💡A new RES Success Story about new reactivity predictions💡

📋 "Exploring the enantioconvergent polycyclization of linear terpenoids catalyzed by Squalene Hopene Cyclase" by the group of Sílvia Osuna from Universitat de Girona

Enzymes can be used to uniquely perform reactions in a selective manner. Recently, in collaboration with Prof. Hauer's team from Johannes Gutenberg-Universität Mainz, they reported the ability of aaSHC (a membrane protein from *Alicyclobacillus acidocaldarius*) to, starting from a 50/50 mixture, produce the exact same single stereoproduct of the industrially-relevant compound Ambroxide.

The project focused on exploring the cyclization of both homofarnesol isomers using QM/MM metadynamics simulations, given the potential that this amazingly rare phenomenon held.

🖥️ Thanks to RES supercomputer #MareNostrum5 from Barcelona Supercomputing Center, the team could calculate more than 6 nanoseconds of metadynamics, producing a detailed free energy surface of the process.

The free energy barriers confirmed that the process is enantioconvergent. In comparison with the equivalent gas-phase reaction, the active site pocket of the protein restricts the flexibility of homofarnesol and favors the production of only one of the stereoproducts. They will further study which specific amino acids of the enzyme are responsible for this phenomenon.

📸 The image shows the free energy landscapes of the polycyclization of homofarnesol, either from the cis or trans configuration, in the active site of Squalene Hopene Cyclase (AaSHC). All energies are expressed in kcal/mol.