17-ERACoBioTech Enzyme platform for the synthesis of chiral aminoalcohols

17-ERACoBioTech 用于合成手性氨基醇的酶平台

• 批准号: BB/R021627/1
• 负责人: John Ward
• 金额: $ 55.71万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FR021627%2F1
• 关键词: 17; ERACoBioTech; Enzyme; platform; synthesis

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.

通过“经典”化学和催化进行的工业化学过程通常涉及使用有害物质、使用大量能源并产生有毒废物。相比之下，酶以精湛的选择性、无与伦比的速率加速和温和的反应条件来催化分子的自然“制造和修饰”。工业生物技术是应用酶催化工业反应的关键使能技术，有潜力按照绿色化学的概念和原则改进化学工艺，并将经济与社会和环境方面全面结合起来。许多成功的工业化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工艺来提供大宗化学品。然而，一些缺点阻碍了生物技术在可持续生物经济方面的全部潜力，例如缺乏足够广泛的酶平台和较长的开发时间表。这些限制对于具有多个手性中心的化合物（例如氨基醇）的合成特别相关，氨基醇是在许多生物活性天然产物（例如生物碱）中发现的部分。氨基醇因其生物活性而非常重要，并且可作为药物和农用化学品合成的手性结构单元。对映体纯的氨基醇的合成很难通过化学方法实现，并且通常需要繁琐的路线，涉及不经济的保护基操作步骤。尽管已经报道了单个目标氨基醇的生物催化合成，但尚未开发出系统地获得结构广泛且立体化学多样化的氨基醇组的连贯策略。为了克服这些缺点，多学科联盟 TRALAMINOL 将重点开发基于两类反应类型的强大的两步生物催化策略： 该方法利用催化碳-碳 (C-C) 键形成的关键酶（生成酮醇），然后由于酶的化学选择性、区域选择性和对映选择性，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强大的工业生物催化平台。这两种关键酶类型的进一步深入开发，以及创建可持续制造多功能手性结构单元的集成反应平台，将显着增强欧洲化学和制药行业的全球竞争力，并加速从对化石能源的依赖转变原材料走向可持续的生物经济。

项目成果

Novel transaminases from thermophiles: from discovery to application.

• DOI: 10.1111/1751-7915.13940
• 发表时间: 2022-01
• 期刊: Microbial biotechnology
• 影响因子: 5.7
• 作者: Cárdenas-Fernández M;Sinclair O;Ward JM
• 通讯作者: Ward JM

The Discovery of Imine Reductases and their Utilisation for the Synthesis of Tetrahydroisoquinolines.

• DOI: 10.1002/cctc.202201126
• 发表时间: 2023-02-08
• 期刊: CHEMCATCHEM
• 影响因子: 4.5
• 作者: Cardenas-Fernandez, Max;Roddan, Rebecca;Carter, Eve M.;Hailes, Helen C.;Ward, John M.
• 通讯作者: Ward, John M.

Characterisation of a hyperthermophilic transketolase from Thermotoga maritima DSM3109 as a biocatalyst for 7-keto-octuronic acid synthesis.

• DOI: 10.1039/d1ob01237a
• 发表时间: 2021-07-28
• 期刊: Organic & biomolecular chemistry
• 影响因子: 3.2
• 作者: Cárdenas-Fernández M;Subrizi F;Dobrijevic D;Hailes HC;Ward JM
• 通讯作者: Ward JM