17-ERACoBioTech Enzyme platform for the synthesis of chiral aminoalcohols

通过“经典”化学和催化进行的工业化学过程往往涉及使用危险物质、消耗大量能源和产生有毒废物。相比之下，酶催化分子的自然“制造和修饰”具有精致的选择性、无与伦比的速度加速和温和的反应条件。工业生物技术，即应用酶催化工业反应，作为一项关键的使能技术，遵循绿色化学的概念和原则，具有改善化学过程的潜力，并将经济与社会和环境方面有机地结合在一起。许多成功工业化的例子包括通过不同的酶合成手性精细化学品，以及使用固定化全细胞和生物合成过程来提供大宗化学品。然而，几个缺点阻碍了生物技术对可持续生物经济的全部潜力，例如缺乏足够广泛的酶平台和较长的开发时间。这些限制特别适用于合成具有多个手性中心的化合物，如氨基醇，这是许多生物活性天然产物中的一种部分，如生物碱。氨基醇具有很高的生物活性，是合成药物和农用化学品的手性构件。合成对映体纯的氨基醇很难通过化学方法实现，通常需要繁琐的路线，包括不经济的保护基团操作步骤。虽然已经报道了单个目标氨基醇的生物催化合成，但还没有开发出系统地获得结构广泛和立体化学多样化的氨基醇集合的连贯策略。为了克服这些缺点，多学科联盟TRALAMINOL将专注于开发仅基于两类反应类型的强大的两步生物催化策略：由于酶的化学、区域和对映体选择性，该方法利用催化碳-碳(C-C)键形成(生成酮醇)的关键酶，然后以高度受控的方式进行氨基转移(生成氨基醇)。允许获得所有可能的对映体的每种类型的酶组合将被开发为一个强大的工业生物催化平台。这两种关键酶类型的进一步密集开发，以及为可持续制造多功能手性构建块而创建的集成反应平台的创建，将显著增强欧洲化工和制药行业的全球竞争力，并加快从依赖化石原材料向可持续生物经济的过渡。

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.