Innovative Routes to Monoterpene Hydrocarbons and Their High Value Derivatives

将化学品/天然产品生产推向“绿色”和更可持续的制造过程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过程相结合。SynBio是一项潜在的颠覆性技术，但在SynBio化学制造取代传统制造工艺之前，需要进行重大的风险降低。这部分反映在与工业部门发展新制造工厂有关的主要费用上，这需要从传统的以石油化学/自然资源为基础的制造过渡到以合成生物为基础的化学品制造。在这个项目中，我们将设计、构建和整合新的SynBio技术，加速为化学品/天然产物合成定制SynBio解决方案的交付。我们的重点是一组具有工业价值的化合物，单萜类化合物，它为使用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类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（如酶催化剂、转运体、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。迭代设计-构建-测试-部署生命周期将用于优化单萜类化学品在定义的原理验证项目中的生产。通过这些示范项目，我们将为化学品/天然产物的生物合成提供创新的SynBio方法，并促进领先的能力开发，从而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）和由申请人团队代表的协作工作文化。酶催化合成生物是有吸引力的：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相结合，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过程中的产品被认为是“天然的”。这增加了显著的市场价值，特别是在食品和调味品制造方面，就像单萜类化合物的生产和使用一样。我们开发的SynBio方法还将产生传统合成方法难以获得的新化学实体。这将为工业开发提供新的机会，包括合成新的化学文库，这将支持工业和学术药物发现计划。更广泛地说，该计划将提供通用工具、技术平台和SynBio“专有技术”，这将广泛影响化学品和天然产品的可持续生产，并降低SynBio方法的风险，以便工业部门更快地采用和发展。

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.