Innovative Routes to Monoterpene Hydrocarbons and Their High Value Derivatives

单萜烃及其高价值衍生物的创新路线

• 批准号: BB/M000354/1
• 负责人: Nigel Scrutton
• 金额: $ 387.23万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM000354%2F1
• 关键词: Innovative; Routes; Monoterpene; Hydrocarbons; Their

Propelling chemicals/natural products production towards 'green' and more sustainable manufacturing processes will require the harnessing of the power of Synthetic Biology (SynBio) and integration with more traditional biocatalytic and chemo-catalytic processes. SynBio is a potentially disruptive technology, but major de-risking is required before the SynBio of chemicals manufacture can replace traditional manufacturing processes. In part, this is reflected in the major costs associated with the development of new manufacturing plant in the industrial sector, which is required to transition from conventional petrochemical/natural resource-based manufacturing to SynBio-based chemicals manufacturing.In this programme we will design, build and integrate new SynBio technology that accelerates delivery of bespoke SynBio solutions for chemicals/natural products synthesis. Our focus is on a major group of industrially valuable compounds, the monoterpenoids, which offer new opportunities for bio-based production using SynBio. By adopting modular 'plug-and-play' platform approaches and a production pipeline that embraces the 'design-build-test-deploy' life-cycle we will turn knowledge assets into innovative chemicals production solutions for monoterpenoid compounds. We will recruit and design bespoke biological parts (e.g. enzyme catalysts; transporters; membrane components) and assemble them in novel ways to create a bio-based production pipeline contained within a synthetic, engineered microbial biofactory. Iterative design-build-test-deploy life-cycles will be used to optimise production of monoterpenoid chemicals in defined proof-of-principle projects. Using these Demonstrator Projects, we will deliver innovative SynBio approaches for chemicals/natural products biosynthesis and promote leading capability development that will stimulate interactions with industry and other stakeholders. These projects will require the unique, multidisciplinary environment (including bioscience, engineering, chemistry and computational science) and collaborative working culture represented by the team of applicants. Enzyme-catalysed SynBio-based synthesis is attractive: regio- and stereo-selective biotransformation, use of 'green' reaction conditions and lack of toxic by-products combine to make biosynthesis attractive in sustainable manufacturing. US and European legislation acknowledges that products from biosynthetic manufacturing processes are considered 'natural'. This adds significant market value, especially in foods and flavourings manufacture, as is the case in the production and use of monoterpenoids. The SynBio approaches we develop will also generate new chemical entities not readily accessible using traditional synthetic approaches. This will provide new opportunities for industrial exploitation, including the synthesis of new chemical libraries that will support industrial and academic drug discovery programmes. More broadly, the programme will provide general tools, technology platforms and SynBio 'know-how' that will impact widely in sustainable manufacture of chemicals and natural products and de-risk SynBio approaches for more rapid take-up and development by the industrial sector.

推动化学品/天然产品生产走向“绿色”和更可持续的制造工艺将需要利用合成生物学（SynBio）的力量，并与更传统的生物催化和化学催化工艺相结合。SynBio是一种潜在的颠覆性技术，但在化学品制造的SynBio取代传统制造工艺之前，需要进行重大的风险消除。在此项目中，我们将设计、构建和整合新的SynBio技术，加快为化学品/天然产物合成提供定制的SynBio解决方案。我们的重点是一组重要的具有工业价值的化合物，即单萜类化合物，它们为使用SynBio进行生物基生产提供了新的机会。通过采用模块化的“即插即用”平台方法和包含“设计-构建-测试-部署”生命周期的生产管道，我们将把知识资产转化为单萜化合物的创新化学品生产解决方案。我们将招募和设计定制的生物部件（例如酶催化剂;转运蛋白;膜组件），并以新颖的方式组装它们，以创建包含在合成工程微生物生物工厂中的生物基生产管道。迭代的设计-构建-测试-部署生命周期将用于在定义的原理验证项目中优化单萜类化学品的生产。利用这些示范项目，我们将为化学品/天然产物生物合成提供创新的SynBio方法，并促进领先的能力发展，促进与行业和其他利益相关者的互动。这些项目将需要独特的多学科环境（包括生物科学，工程，化学和计算科学）和申请人团队所代表的协作工作文化。酶催化的SynBio-based合成是有吸引力的：区域和立体选择性生物转化，使用“绿色”反应条件和缺乏有毒副产物结合联合收割机，使生物合成在可持续制造中具有吸引力。美国和欧洲的立法承认，生物合成制造工艺的产品被认为是“天然的”。这增加了巨大的市场价值，特别是在食品和调味品制造中，如在单萜类化合物的生产和使用中。我们开发的SynBio方法还将产生使用传统合成方法不易获得的新化学实体。这将为工业开发提供新的机会，包括合成新的化学品库，以支持工业和学术药物发现方案。更广泛地说，该计划将提供通用工具、技术平台和SynBio“专业知识”，这将对化学品和天然产品的可持续制造产生广泛影响，并降低SynBio方法的风险，以便工业部门更快地采用和发展。

项目成果

Teaching Enzyme Catalysis Using Interactive Molecular Dynamics in Virtual Reality

• DOI: 10.1021/acs.jchemed.9b00181
• 发表时间: 2019-11-01
• 期刊: JOURNAL OF CHEMICAL EDUCATION
• 影响因子: 3
• 作者: Bennie, Simon J.;Ranaghan, Kara E.;Glowacki, David R.
• 通讯作者: Glowacki, David R.

Emergence of a Negative Activation Heat Capacity during Evolution of a Designed Enzyme

设计酶的进化过程中负活化热容的出现

• DOI: 10.5167/uzh-174733
• 发表时间: 2019
• 作者: Bunzel, H Adrian

From Bugs to Bioplastics: Total (+)-Dihydrocarvide Biosynthesis by Engineered Escherichia coli.

• DOI: 10.1002/cbic.201800606
• 发表时间: 2019-03-15
• 期刊: Chembiochem : a European journal of chemical biology
• 作者: Ascue Avalos GA;Toogood HS;Tait S;Messiha HL;Scrutton NS
• 通讯作者: Scrutton NS

L718Q mutant EGFR escapes covalent inhibition by stabilizing a non-reactive conformation of the lung cancer drug osimertinib.

• DOI: 10.1039/c7sc04761d
• 发表时间: 2018-03-14
• 期刊: Chemical science
• 影响因子: 8.4
• 作者: Callegari D;Ranaghan KE;Woods CJ;Minari R;Tiseo M;Mor M;Mulholland AJ;Lodola A
• 通讯作者: Lodola A

Exploration of the structural requirements of Aurora Kinase B inhibitors by a combined QSAR, modelling and molecular simulation approach.

• DOI: 10.1038/s41598-021-97368-3
• 发表时间: 2021-09-21
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Ashraf S;Ranaghan KE;Woods CJ;Mulholland AJ;Ul-Haq Z
• 通讯作者: Ul-Haq Z