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

Project description

Efficient enzymatic one-pot systems

The biotechnological production relies on enzymatic cascades for complex biotransformations, but efficient, cell-free, one-pot systems with regulated components are not currently available. The EU-funded HOTZYMES project proposes a new concept for the spatio-temporal control over the kinetics of multi-enzymatic cascades via remote alternating magnetic fields. The enzyme activity will be regulated by conjugating enzymes and magnetic nanoparticles and tuning temperature gradients at the nanoscale to precisely and locally reach the optimal temperature of each immobilised enzyme. To ensure easy separation, re-utilisation and integration into bioreactors, these conjugates will be integrated within porous microparticles. Novel magnetic bioreactors specific for biocatalysis will also be designed and fabricated to meet this technological breakthrough.

Objective

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).

Call for proposal

H2020-FETOPEN-2018-2020

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Sub call

H2020-FETOPEN-2018-2019-2020-01

Coordinator

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Net EU contribution
€ 810 532,50
Address
CALLE SERRANO 117
28006 Madrid
Spain

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Region
Comunidad de Madrid Comunidad de Madrid Madrid
Activity type
Research Organisations
Links
Total cost
€ 810 532,50

Participants (7)