AMBIOCAS

AMINE SYNTHESIS THROUGH BIOCATALYTIC CASCADES

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 Obiettivo del progetto (Objective)

'This project intends to engineer transaminase libraries that will be applied as the main enzymatic technology to deliver the amine functionality in the commercially valuable products of both chiral and bulk amine targets. These enzymes will be used in enzymatic cascades where simple starting materials are converted into the required intermediates for transamination or further enzymatic steps will be used to remove products from the transaminase reaction which will add value by extra functionality. This will also be supported by the development of enzymatic cascades to deliver efficient co-factor recycling and achieve the high conversions required for industrial use. A high throughput screening method based on a further enzymatic cascade will be developed. Engineering solutions will be used to overcome obstacles associated with the implementation of this core technology on a larger scale and integrate the use of other enzymes into the synthetic pathway to allow multi-step, multi-enzyme cascades to be used to deliver complex multi-functional amine products and processes. The industrial partner will target the development of enzymes from the project for specific application into their new products range. Life cycle analysis and environmental impact analysis will compare the final methods with conventional chemical synthesis and allow advantages to be objectively defined.'

Introduzione (Teaser)

There is an ongoing quest for safer and cleaner chemical methods to synthesise various compounds. European researchers designed enzymatic cascades that could complement or replace classical chemistry in the development of amine-containing products.

Descrizione progetto (Article)

Amines are important chemical intermediates that are extensively exploited in the production of polymers, pharmaceuticals and other chemicals. A very popular example is 6-aminocaproic acid, a compound used in the production of polyamide polymers in applications such as textiles, floor coverings or other nylon-type products.

The conventional chemical synthesis route entails the use of phenol and has a significant energy and waste pattern. To resolve this, scientists on the EU-funded 'Amine synthesis through biocatalytic cascades' (http://www.ambiocas.eu (AMBIOCAS)) project proposed to synthesise amines by exploiting the catalytic activity of transaminase enzymes.

To this end, various mutant transaminases were genetically engineered and a library was created. These mutants were designed based on the elucidation of the three-dimensional structures of several transaminases by protein X-ray crystallography. The long-term plan was to use these enzymes in biotechnology applications to synthesise amine functional groups in various commercial products.

Following the identification of the transaminase enzymes that would catalyse the conversion to amines, enzymatic cascades were designed for obtaining extra chemical functionality. A series of issues had to be overcome first, including the unfavourable thermodynamic equilibrium of converting a ketone to an amine. Detailed analysis of the kinetics and energy parameters of the reaction led to the optimisation of reaction conditions and enzyme properties. A key innovative step in the AMBIOCAS enzymatic cascade was the co-factor regeneration during the multi-step process without the need for intermediate isolation. Overall, this simplified the synthesis of 6-aminocaproic acid in six enzymatic steps.

Given the high activity and selectivity of enzymes, the AMBIOCAS enzyme-based method holds significant economic benefits with the cleaner synthesis of desired products. This technology will limit the exposure to toxic, flammable and explosive hazards commonly encountered in the chemical industry.