BIOCASCADE

Biocatalytic cascades to access valuable building blocks

 Partecipanti

Mappa

 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

 Obiettivo del progetto (Objective)

'The aim of this project is to provide training in the multidisciplinary fields of organic chemistry, biocatalysis, molecular biology, biochemistry and microbiology to design and develop artificial cascades by combining various types of enzymes such as L-amino acid oxidades, alcohol dehydrogenases and lyases. This is a truly competitive, innovative and timely field in which to work, and for sure the results derived from this cutting-edge project will be published in top ranked journals contributing to European Excellence.

The project is expected to make a major contribution to replace traditional chemical manufacturing which relies in highly toxic, expensive and stoichiometric reagents, many steps and toxic solvents with so-called “white biotechnology” which employs powerful natural biocatalysts such as enzymes or whole cell microorganisms that allow the combination of several steps in one-pot without isolation of intermediates (cascade reactions) establishing environmentally benign and sustainable chemical processes for the preparation of optically active valuable compounds and minimizing the wastes. The research project will be divided in three main research objectives: (i) Enzymatic cascades leading to aminoacids to hydroxyacids: Novel enantioselective routes for the preparation of enantiopure hydroxyacids, (ii) Biocatalytic cascades leading to trans-coumaric acid derivatives, (iii) Redox-neutral cascade coupling of lactate to phenol via C-C bond formation. Applications to natural product synthesis.

The optimal development of the project is guaranteed by the high quality of the host institution (University of Graz) and the supervisor (Prof. Wolfgang Kroutil). The host institution owns all the facilities and infrastructures that are required for the performance of this interdisciplinary project while Prof. Kroutil is a world-leading scientific in the field of biocatalytic cascade transformations with well established collaborations with world-class researchers.'

Introduzione (Teaser)

The chemical industry supports numerous sectors of the EU economy, providing the building blocks for new materials, processes and products. Novel 'one-pot' synthetic cascades utilising natural enzymes will support more competitive and sustainable production.

Descrizione progetto (Article)

Traditionally, industrial chemical production has relied on harsh, often toxic and expensive reagents and solvents in processes requiring multiple steps. White biotechnology relying on powerful natural biocatalysts such as enzymes or whole-cell microorganisms can achieve multiple reaction steps in a single pot (cascade reactions) without the need to isolate intermediates.

The EU-funded training project BIOCASCADE (Biocatalytic cascades to access valuable building blocks) focused on white biotechnology for the preparation of compounds with applications to natural product synthesis and building blocks for advanced materials. Extensive multidisciplinary training formed the foundation for the project's success.

Team members developed a biocatalyst-based simultaneous oxidation-reduction cascade to transform natural ?-amino acids into valuable ?-hydroxy acids, important in commercial products, including exfoliators for skin care. Co-expression of the required biocatalysts in the same plasmid improved the methodology with a focus on industrial applications. This part of the work has resulted in two publications in peer-reviewed scientific journals.

Another single-pot reaction attacked a particularly difficult reaction type for which no chemical or single-step enzymatic transformation is available, namely the para-vinylation of phenols. The team successfully combined carbon-carbon (C-C) bond-creating enzymes with C-nitrogen bond-breaking enzymes. The resulting specific and selective functionalisation of phenols provides access to highly valuable chemical building blocks. Given the groundbreaking nature of the result, a patent application has been filed and the results have been accepted in a peer-reviewed high impact journal.

Finally, a four-step cascade combining C-C bond-creating enzymes and oxidoreductases has been established for the production of aryl lactic acids. These natural building blocks are of particular interest to the pharmaceutical and cosmetics industries. Scientists are currently preparing a manuscript to share the results.

BIOCASCADE has led to new one-pot synthesis methods for natural products based on white biotechnology. The results will have important impact on the competitiveness and sustainability of the EU chemical industry while facilitating development of more eco-friendly products for consumers.