Hydroxylierung - Biocatalysis for the hydroxylation of aliphatic heterocyclic chemical building blocks

Background. Functionalized derivatives of heterocyclic five-membered ring structures belong to the most important chiral building blocks for manufacturing of pharmaceuticals, agrochemicals, cosmetics, and natural compounds. The project aims at replacing waste-intensive chemical routes for the synthesis of these important fine chemicals by biohydroxylation, employing substrates and organic solvents from renewable resources. The proposed research is a response to the strong need for novel greener approaches for the selective oxyfunctionalization of biobased and conventional chemical scaffolds and intermediates. Main objectives. Selective hydroxylations are among the most difficult chemical reactions but enable important direct and indirect functionalization of non-activated C-H bonds to generate key intermediates for chemical synthesis. With this proposal, we specifically address biobased solutions for the direct hydroxylation in the electronically unfavored 3 position of five-membered heterocyclic rings. To our knowledge, there are no currently available economic solutions by metal catalysis to this reaction. The proposed research investigates the biochemical properties and implements the biocatalytic potential of the robust cytochrome P450 family CYP153, aiming at three specific goals: · access to and development of efficient and selective enzymes for the hydroxylation of simple heterocyclic five-membered ring structures; · biohydroxylation using substrates and solvents from renewable resources; · demonstration of the feasibility of biotransformations with commercially useful yields. By targeting to apply a comparatively unexplored enzyme class to a specifically challenging reaction, the project combines innovative solutions to industrial challenges with scientific progress in a competitive field of biological chemistry. An international, highly complementary and multidisciplinary team. We will take advantage of the complementary expertise of two participating laboratories, Mattevi’s group in Pavia and the Glieder and Nidetzky groups at the Graz University of Technology, and of the collaboration with Dr. Dr. Z. Li at the National University in Singapore. In a cross-disciplinary approach that combines research in enzymology, organic syntheses, cutting-edge molecular botechnology methods with the joint experience and knowledge in oxygenase-catalyzed biotransformations from previous and ongoing collaborations, we will provide key enabling technologies for bio-based fine chemical industry which has important production sites in northern Italy. Dissemination and social impact. The project integrates to the bioeconomy chain value by delivering new applications that take advantage of bioderived organic solvents and attractive starting materials for biochemical synthesis and applying nature derived tools for manufacturing. The workplan has a strong emphasis on biobased solutions to support the Italian fine chemical industry with new production technologies and on providing young trained scientists with industrially relevant skills in bioeconomy and technology transfer as well as giving them opportunities to find adequate jobs. Along this line, the proposal has a clear commitment to disseminate and maximize the visibility of the research. The goal is to create a win-win situation by intensifying the already ongoing research collaborations between Universities of Pavia and Graz and their local and international industry networks.