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危险物质，使用大量能量并产生有毒废物。相反，酶以精致的选择性，无与伦比的速率加速度和轻度反应条件下催化分子的天然“制造和修饰”。工业生物技术，酶在催化工业反应中的应用，作为一种关键的促成技术，有可能根据绿色化学的概念和原理来改善化学过程，并将经济学与社会和环境方面整体结合。许多成功工业化的例子包括通过不同的酶合成手性的化学物质，以及使用固定的全细胞和生物合成过程来提供散装化学物质。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表。这些限制与具有多个手性中心的化合物（例如氨基醇）特别相关，例如氨基醇，这是在许多生物活性天然产物（例如生物碱）中发现的部分。氨基醇由于其生物活性而非常重要，并且起着药物合成的手性构建块的作用。化学方法很难实现对映体纯氨基醇的合成，并且通常需要涉及保护性群体操作的不经济步骤的繁琐途径。尽管已经报道了单个靶氨基醇的生物催化合成，但尚未制定系统地进入结构宽和立体化学上多样化的氨基醇。为了克服这些弊端，多学科曲纳米诺醇将基于两种反应类型的强大两步生物催化策略的发展，以催化碳碳（C-C）键形成的关键酶（创建酮酒精），以促进氨基烷酸（促成氨基烷），以促进氨基化的含量（C-c），以促进氨基烷酸（in in ominotrans），以促进氨基转运（in Contranoty）。区域和对映选择性。允许访问所有可能对映异构体的每种类型的酶投资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强烈开发，以及为可持续制造多功能手性构建块的综合反应平台的创建，将显着增强欧洲化学和制药行业的全球竞争力，并加速从对化石原料转向可持续生物学经济体的依赖性的过渡。

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