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Biocatalytic cascades to access valuable building blocks

Final Report Summary - BIOCASCADE (Biocatalytic cascades to access valuable building blocks)

The aim of this project “Biocascade” was to develop cleaner and more efficient chemical processes based on the combination of several enzymatic reactions in one-pot without isolating the reaction intermediates. The use of enzyme catalysts is intrinsically environmentally friendly and has been successfully applied for the replacement of toxic processes in the preparation of valuable building blocks. For the successful development of the project, the research group of Prof. Kroutil provided to the researcher an extensive training in the fields of molecular biology, asymmetric synthesis, biochemistry, microbiology and synthetic organic chemistry. By using this techniques, in the first part of the project natural alpha-amino acids were transformed to valuable alpha-hydroxy acids by a biocatalytical simultaneous oxidation reduction cascade (Chem. Eur. J. 2014, 20, 11225-11228). This methodology was later improved for industrial applications with a synthetic biology strategy which allowed co-expressing the required biocatalysts in a single expression plasmid (Chem. Commun. 2015, DOI:10.1039/c4cc08286a). In the second section of the project, C-C bond creating enzymes (EC 4.1) C-N breaking enzymes (EC 4.3) were combined for the regioselective p-functionalization of phenols that provided access to highly valuable building blocks (2 manuscripts in preparation), for which no chemical or single step enzymatic equivalent to this transformation is available; For this reason, a patent is currently be filed to properly guarantee the intellectual property of this finding. Finally, a four step cascade was established for the production of pharmacologically relevant aryl lactic acids combining C-C bond creating enzymes (EC 4.1) and oxidoreductases (one manuscript in preparation). The state of the art in the field of biocatalytical cascades has also been recently reviewed in collaboration with the rest of the group (ACS Catal. 2014, 4, 129-143).
Moreover, the excellent working environment in Kroutil´s lab allowed a close interaction between the fellow and different members of the group using different types of biocatalysts for the preparation of valuable organic compounds. As a result, three research articles have been recently published in high impact journals (ω-TAs, Adv. Synth. Catal. 2014, 356, 1937-1942; ADHs, Eur. J. Org. Chem. 2014, 111-121; Organocatalysis + ADHs, Chem. Commun. 2014, 50, 15669-15772).
In this period, the researcher also received an additional training that will be essential for his future career including the supervision of students (undergraduated, visiting and Bachelor), practising presentation skills (regular seminars and international conferences), reporting skills (quarterly reports) and taking responsibilities in the research group (maintenance of laboratories and instruments).
Without any doubt, this grant gave to the researcher an excellent opportunity for reaching a position of professional maturity. In this sense, thanks to the excellent work developed in this grant, the researcher was selected in a competitive call (MINECO, Spain) for a University assistant position (Juan de la Cierva programme, Universidad Complutense, Madrid).