Project: Enzyme platform for the synthesis of chiral aminoalcohols

Acronym	TRALAMINOL (Reference Number: 64)
Duration	01/04/2018 - 31/03/2021
Project Topic	Amino alcohol moieties are found in highly diverse classes of natural products that are of great importance due to their bioactivity, and they function as chiral building blocks for the synthesis of pharmaceuticals and agrochemicals. The chemical synthesis of stereoisomerically pure amino alcohols is difficult and typically requires uneconomical steps for protective group manipulations. Conventional syntheses in the chemical industry often use hazardous substances, consume large amounts of energy and generate toxic waste. The TRALAMINOL project will address the challenges with the innovative development of sustainable biotechnological processes for the synthesis of amino alcohols through a multi-disciplinary approach.The consortium assembles leading European research groups (Germany, UK, Spain, France) with different but complementary scientific and technological expertise (4 non-profit organizations, 1 SME, 1 large company). TRALAMINOL will focus on the development of a powerful one-pot two-step biocatalytic strategy based on only two classes of reaction types: The approach makes use of key enzymes that catalyze C–C bond formation followed by enzymatic amino transfer in highly controlled fashion by exploiting the enzymes’ high chemo-, regio- and enantioselectivity, while operating under mild reaction conditions. The project will span TRL 3-7 by incorporating demonstration reactions at technical scale (up to 10L reactor volume) carried out by industrial partners. The reaction cascades are designed so that the choice of substrate and specificity of the enzymes involved will generate different target structures in a controlled fashion. At an advanced stage this technology may be transferred into recombinant whole-cell catalysts to improve overall economics for industrial applications. Substrates are bio-based, sustainable building blocks that will be transformed into molecules with high added value. Compounds with low water solubility can be addressed by the use of solvent stable enzymes from thermophiles. The consortium has identified a series of relevant target structures from different compound classes that are important representatives for diverse billion-€ pharmaceutical market segments, including drugs related to treatment of cancer, circulatory disease, diabetes, microbial infection and others. With its one third industrial participation and top-down approach to identified market needs, the consortium not only represents academic excellence but also covers commercial interests at different stages of the value chain. Thus, the processes developed within the TRALAMINOL project and evaluated against their economic viability can achieve a significant environmental impact by replacing more energy and resource intensive processes, leading to reduced environmental footprints and lowering our dependence on fossil raw materials. Enzyme portfolios of each reaction type designed for maximum genetic diversity will be developed as a robust industrial biocatalytic platform. Such superfamily panels will be manufactured by a unique technology platform for massive recombinant protein expression and production, enabling gram quantities of 1000s of enzymes. Such carefully designed enzyme selection panels significantly reduce the time and effort required to identify the best catalyst for novel target substrates. Further intense development of these two critical enzyme types, and the creation of an integrated reaction platform for the sustainable manufacture of multifunctional chiral building blocks, will significantly strengthen the global competitiveness of the European chemical and pharmaceutical industries and accelerate the transition from a dependence on fossil raw materials toward a sustainable bio-based economy.
Project Results (after finalisation)
Website	visit project website
Network	ERA CoBioTech
Call	ERA CoBioTech “Biotechnology for a sustainable bioeconomy”

Project partner

Number	Name	Role	Country
1	Technische Universität Darmstadt	Coordinator	Germany
2	Consejo Superior de Investigaciones Científicas - Institute of Advanced Chemistry of Catalonia	Partner	Spain
3	Université Clermont Auvergne	Partner	France
4	University College London	Partner	United Kingdom
5	PROZOMIX	Partner	United Kingdom
6	BASF SE	Partner	Germany