HOTZYMES · Redesigning biocatalysis: Thermal-tuning of one-pot multienzymatic cascades by nanoactuation

Enzymatic cascades open a path to the efficient implementation of complex biotransformations for producing from high-cost pharmaceuticals to low-cost biocommodities. However, for multi-step synthetic schemes catalyzed by incompatible or unpaired enzymatic cascades, efficient cell-free one-pot systems, where enzymes are perfectly orchestrated and regulated, have yet to be developed. In HOTZYMES, we propose to develop a new ground-breaking concept to exert functional control over different enzymes using magnetic heating. We expect to control enzyme activity by conjugating enzymes and magnetic nanoparticles and tuning temperature gradients at the nanoscale to precisely and locally reach the optimal temperature of each immobilized enzyme. This will allow an unprecedented spatio-temporal control over the kinetics of multi-enzymatic cascades by remotely applying alternating magnetic fields. To ensure an easy separation, re-utilization and integration into bioreactors, these conjugates will be integrated within porous microparticles. To meet this technological break-through we will need to design and fabricate a new generation of magnetic bioreactors specific to the field of Biocatalysis. We will need to answer fundamental questions about the physical mechanisms that govern heat transfer/diffusion between magnetic materials and biomolecules at different spatial scales by bringing together different scientific and technological disciplines and expertise. HOTZYMES will thus contribute to change current industrial biotransformations from an unsatisfactory current paradigm (uncoordinated enzyme function, sequential reactions, disposable bioprocesses) into a game-changing breakthrough (coordinated enzyme function, concurrent reactions, recyclable bioprocesses).