17-ERACoBioTech Enzyme platform for the synthesis of chiral aminoalcohols

点击翻译按钮获取中文摘要

Industrial chemical processes carried out through "classic" chemistry and catalysis often involve the use of hazardous substances, use considerable amounts of energy and generate toxic waste. In contrast, enzymes catalyze the natural "manufacture and modification" of molecules with exquisite selectivity, unparalleled rate acceleration and under mild reaction conditions. Industrial Biotechnology, the application of enzymes to catalyze industrial reactions, as a Key Enabling Technology has the potential to improve chemical processes in compliance with the concept and principles of Green Chemistry and holistically combines economics with social and environmental aspects. Many successfully industrialized examples include the synthesis of chiral fine chemicals by means of different enzymes, as well as the use of immobilized whole-cells and biosynthetic processes for the provision of bulk chemicals. Yet, several drawbacks hinder the full potential of biotechnology for a sustainable bioeconomy, such as the lack of a sufficiently broad range of enzyme platforms and long development timelines. These restrictions are particularly relevant for the synthesis of compounds having multiple centers of chirality such as amino alcohols which is a moiety found in many bioactive natural products such as alkaloid. Amino alcohols are highly important due to their bioactivity, and function as chiral building blocks for the synthesis of pharmaceuticals and agrochemicals. The synthesis of enantiomerically pure amino alcohols is difficult to achieve by chemical approaches and typically requires tedious routes involving uneconomical steps for protective group manipulations. Although the biocatalytic synthesis of individual target amino alcohols has been reported, no coherent strategy for a systematic access to structurally broad and stereochemically diverse sets of amino alcohols has been developed yet. To overcome these drawbacks, the multidisciplinary consortium TRALAMINOL will focus on the development of a powerful two-step biocatalytic strategy on the basis of only two classes of reaction types: The approach makes use of key enzymes that catalyze carbon-carbon (C-C) bond formation (to create keto alcohols) followed by aminotransfer (to create amino alcohols) in highly controlled fashion due to the enzymes' chemo-, regio- and enantioselectivity. Enzyme portfolios of each type that allow access to all possible enantiomers will be developed as a robust industrial biocatalytic platform. 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.