Non-Enzymatic Catalysis in the Microbial Cell Interior

微生物细胞内部的非酶催化

• 批准号: MR/S033882/1
• 负责人: Stephen Wallace
• 金额: $ 153.76万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FS033882%2F1
• 关键词: Non; Enzymatic; Catalysis; Microbial; Cell

Reducing our society's reliance on non-renewable fossil fuels is arguably one of the most important challenges facing the modern chemical industry.Traditionally, the fields of synthetic organic chemistry and metabolic engineering have represented two independent solutions to this challenge. Whereas synthetic organic chemists use largely non-biological reagents to manipulate small molecules in multi-step processes, metabolic engineers encode synthetic pathways within a sequence of DNA and overproduce target compounds via fermentation. However, despite the respective (and potentially complementary) benefits of these two approaches, metabolic engineering and synthetic organic chemistry have existed as largely separate disciplines for over a century. This Fellowship will merge these two fields by developing non-biological reactions for use within metabolically engineered microbial cells. It will, uniquely, focus on exploring these reactions in the cell interior and within designer metabolic pathways. Reactions will be targeted to various compartments of the cell using a "click" reaction between the catalyst scaffold and a genetically-encoded unnatural amino acid. Ultimately, this will enable microbial cells to synthesise molecules that are not found in Nature and therefore cannot be genetically encoded. In doing so, this will also answer fundamental questions in the field, namely:(i) Can non-enzymatic catalysis be truly integrated within an engineered metabolic pathway?(ii) Can interactions between chemical catalysts and biomolecules within the cell enhance catalysis in vivo? (iii) If so, can the chemical environment of the cell interior support modes of catalysis that are currently not possible in organic solvent? Overall, this approach represents a unique solution to the problem of renewable chemical manufacture and will dramatically increase the range of small molecules that can be produced from biological feedstocks using engineered microbial cells.

减少我们社会对不可再生化石燃料的依赖可以说是现代化学工业面临的最重要的挑战之一。传统上，合成有机化学和代谢工程领域代表了这一挑战的两个独立解决方案。合成有机化学家主要使用非生物试剂在多步过程中操纵小分子，而代谢工程师在DNA序列中编码合成途径，并通过发酵过量生产目标化合物。然而，尽管这两种方法各自（和潜在的互补）的好处，代谢工程和合成有机化学已经存在了世纪作为很大程度上独立的学科。该奖学金将通过开发用于代谢工程微生物细胞的非生物反应来合并这两个领域。它将独特地专注于探索细胞内部和设计代谢途径中的这些反应。使用催化剂支架和遗传编码的非天然氨基酸之间的“点击”反应，反应将靶向细胞的各个隔室。最终，这将使微生物细胞能够合成自然界中没有的分子，因此无法进行遗传编码。在这样做的过程中，这也将回答该领域的基本问题，即：（i）非酶催化能否真正整合到工程代谢途径中？(ii)细胞内化学催化剂和生物分子之间的相互作用能增强体内催化作用吗？(iii)如果是这样的话，细胞内部的化学环境是否能够支持目前在有机溶剂中不可能的催化模式？总的来说，这种方法代表了可再生化学品制造问题的独特解决方案，并将大大增加使用工程微生物细胞从生物原料生产的小分子的范围。

项目成果

Bread waste - A potential feedstock for sustainable circular biorefineries.

• DOI: 10.1016/j.biortech.2022.128449
• 发表时间: 2022-12
• 期刊: Bioresource technology
• 影响因子: 11.4
• 作者: Vinod Kumar;P. Brancoli;Vivek Narisetty;Stephen Wallace;D. Charalampopoulos;Brajesh Kumar Dubey;Gopalakrishnan Kumar;Amit Bhatnagar;Shashi Kant Bhatia;Mohammad J Taherzadeh

Engineering biology for sustainable 1,4-butanediol synthesis.

• DOI: 10.1016/j.tibtech.2023.01.006
• 发表时间: 2023-01
• 期刊: Trends in biotechnology
• 影响因子: 17.3
• 作者: Connor L. Trotter;G. S. Babu;Stephen Wallace

Microbial synthesis of vanillin from waste poly(ethylene terephthalate).

• DOI: 10.1039/d1gc00931a
• 发表时间: 2021-07-05
• 期刊: Green chemistry : an international journal and green chemistry resource : GC
• 作者: Sadler JC;Wallace S
• 通讯作者: Wallace S

Biocompatible a-Methylenation of Metabolic Butyraldehyde in Living Bacteria

活细菌中代谢丁醛的生物相容性α-甲基化

• DOI: 10.1002/ange.202306347
• 发表时间: 2023
• 期刊: Angewandte Chemie
• 作者: Dennis J

Palladium Nanoparticles from Desulfovibrio alaskensis G20 Catalyze Biocompatible Sonogashira and Biohydrogenation Cascades.

• DOI: 10.1021/jacsau.2c00366
• 发表时间: 2022-11-28
• 期刊: JACS AU
• 影响因子: 8
• 作者: Era, Yuta;Dennis, Jonathan A;Horsfall, Louise E;Wallace, Stephen
• 通讯作者: Wallace, Stephen