Periodic Reporting for period 1 - HOTZYMES (Redesigning biocatalysis: Thermal-tuning of one-pot multienzymatic cascades by nanoactuation)
Reporting period: 2019-04-01 to 2020-03-31
The use of multi-enzyme processes for in vitro synthetic biology is currently considered a promising biomanufacturing platform. Enzymatic cascades open a path to the efficient implementation of complex biotransformations for the production of high-cost pharmaceuticals to low-cost biocommodities. They are valuable alternative routes to traditional step-wise chemical synthetic processes, since substrate specificity, stereo- and regioselectivity of enzymes are outstanding. This allows to circumvent the isolation of by-products and reaction intermediates and, thus, to increase the eco-efficiency of the overall process. Besides, one-pot multi-enzyme biocatalysis has numerous manufacturing advantages, such as higher product yield, faster reaction rates, less energy input needed and less waste generation. Unfortunately, the development of efficient cell-free metabolic systems perfectly orchestrated and regulated is still an unmet need.
- Why this is important for society?
In addition to a clear potential economic impact, the development of well-coordinated one-pot enzymatic cascades of industrial interest is a fundamental pillar in the roadmap for the transition from a fossil fuel-based economy to a bio-economy based on climate change.
- What are HOTZYMES overall objectives?
HOTZYMES overall objective consists in the establishment of a new ground breaking concept to exert functional control over different enzymes using magnetic heating in well coordinated one-pot-systems. Its achievement will pave the road for changing 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). This would enable in the long term to accomplish a quantum leap in the production of pharmaceuticals or biobased chemicals.
In this sense, HOTZYMES partners expect to develop a new ground breaking concept to provide optimal reaction conditions for different enzymes, to ultimately implement efficient multienzyme “one-pot” processes of industrial interest. In particular, it is expected to achieve the magnetic-driven remote control of three different enzymatic bioprocesses for obtaining from high-value intermediates in the synthesis of drugs (eg. antitumoral, antiparasitic, anticholinergic, etc) to a zero-calorie sweetener with probiotic activity. In all cases, their chemical synthesis is highly inefficient and thus, this is a great opportunity to tackle their production in a more efficient way.
Thus, the accomplishment of the goals herein proposed has clear potential economic impact. Specifically, it will engender modernity among the industrial biotechnology community, solving current challenges that are hampering the development of new, sustainable, eco-efficient and competitive biocatalytic ex-vivo cascades to access high added-value products. Thus, HOTZYMES´s vision is clearly aligned with that of Paris protocol of transforming industrial biocatalysis into the blueprint for tackling global climate change beyond 2020.