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Light-driven sustainable biocatalysis training network

Periodic Reporting for period 1 - PhotoBioCat (Light-driven sustainable biocatalysis training network)

Reporting period: 2018-01-01 to 2019-12-31

Pharmaceutical and chemical products present in everyday life are currently obtained from waste- and energy-intensive processes. Alternative routes that overcome this waste challenge should offer a cleaner and long-lasting solution. PhotoBioCat aims at developing efficient and sustainable light-driven enzyme-catalyzed chemical processes to a commercial industrial level. The PhotoBioCat EJD trains 12 early-stage researchers (ESRs) in cutting edge research projects on (i) the development of chemical and biological catalytic systems for the synthetic use of visible light for the production of pharmaceuticals, bulk-, fine- and specialty chemicals, (ii) up-scaling and optimization of commercially relevant processes together with industry, (iii) defining a road-map for the industrial implementation of photobiocatalysis. A double degree program allows in-depth training in two complementary disciplines, further strengthened by a transferable skills training with strong industry participation. The objectives will be attained through a consortium of seven universities and eight industrial partners, providing the ideal environment to foster complementary expertise in chemical synthesis, biocatalysis, synthetic biology and process engineering. PhotoBioCat will explore (a) the catalytic application of photosynthetic microorganisms and their optimization by modern synthetic biology techniques; (b) the coupling of enzymes to light-harvesting molecules in vitro; and (c) the optimization of photobiocatalytic processes to technical scale; accompanied by specially designed training of the ESRs and dissemination & communication of the results to scientific community and public.
After the recruitment of 12 highly talented young scientist, the first phase of the projects was dedicated to the establishment of the experimental systems and the experimental proof of the reaction concepts. The ESRs showed remarkable progress and established several new systems for light-driven biocatalysis in cellular and cell-free systems. Secondments to industry and intensive discussions at project meetings with participants from the private sector allowed a clear orientation of the research for innovation and technical implementation. The double degree structure of the project offered a framework to conduct highly interdisciplinary research at the interface of synthetic biology, chemistry and process engineering.
Work on cyanobacterial whole-cell biocatalysts allowed to expand the scope of the method towards novel enzyme classes, including light-driven imine-reduction for the synthesis of chiral amines. This part of the work generated model systems to compare different enzyme classes and the utilization of different redox cofactors. The first phase of the project was also used to investigate optimal reaction conditions for cyanobacterial biotransformations and to generate mutants that are expected to be improved chassis for whole-cell biocatalysis. The second phase will focus on the integration of the different enzymes to the chassis and to aim for a substantial improvement of productivity and space-time-yield of the reactions of interest.
Work on photobiocatalysis in cell-free systems compared light-driven enzymes with indirect photobiocatalysis using organic and inorganic photocatalysts. The ESRs explored new reaction concepts for the coupling of highly selective enzymes to light-driven supply of redox cofactors. Work spans from the coupling of bacterial whole-cell biocatalysts to photocatalysts in the cell-free space to the investigation of photosynthesis in cell-free systems. After the establishment of the reaction systems and the proof-of-concept, research in the second phase will be dedicated to a detailed investigation of the electron transfer and the development of strategies for an optimization of the reactions at different scales.

The work on the scale-up and intensification focused on different photobiocatalytic strategies for the synthesis of a platform chemical, including light-driven biotransformation in vivo and two different routes using in vitro photobiocatalysis. The results so far highlighted key parameters of the reaction conditions. In the scale-up, the investigation of different reactor concepts is considered crucial for an optimal supply of light for the light-harvesting systems.
The research so far has produced new reactions for photobiocatalysis. Photobiocatalysis allows significant savings in sacrificial cosubstrates, which will greatly improve the atom efficiency of redox biocatalysis. The results of PhotoBioCat are thus expected to contribute to promote biocatalysis as an environmentally-friendly method for the chemical and pharmaceutical industry. PhotoBioCat EJD has created an interdisciplinary discussion and idea exchange platform thanks to the academic secondments to the well-established research laboratories. An important aspect of PhotoBioCat is the intensive interaction with the private sector, which is crucial to convert inventions to innovations. The first phase of PhotoBioCat produced demonstrations how enzymes can be coupled to light-harvesting systems as electron donors for redox biocatalysis. In the second phase, we expect that the interdisciplinary collaboration will increase our understanding how enzyme and light-harvesting systems can be combined in cellular and cell-free systems, and our knowledge on the key parameters for an optimization of these reactions. The interdisciplinary research and the intensive interaction with the private sector are highly positive aspects for the training of 12 talented early-stage-researchers as it will provide them with scientific and transferable skills required to work successfully in a highly dynamic, interdisciplinary and international field and to bring new reaction concepts into the producing industry.
PhotoBioCat Consortium