'13TSB_SynBio' Genome-scale metabolic modelling to optimise high value microbial manufacturing

我们开始看到大规模生物技术的重点从生物燃料（如生物乙醇和生物丁醇）转向精细和散装化学品（如琥珀酸和丙二醇）生产。甲基丙烯酸是生产有机玻璃（也称为Lucite）所用甲基丙烯酸甲酯（MMA）的最广泛使用的起始材料。MMA是甲基丙烯酸酯行业的主要组成部分，并支持全球广泛的供应链。所有这些材料目前都是由石化原料生产的。作为MMA生产的主要参与者（占全球总产量的24%），该项目的参与公司之一Lucite致力于开发基于可再生原料的路线。该项目旨在设计一种工业微生物，以生产商业上可行的甲基丙烯酸酯前体。将微生物的大部分资源用于生产对自身无益的产品，通常涉及其代谢网络的广泛重新调整。剑桥大学的科学家们将构建一个微生物代谢的计算机模型，并将其用于模拟，以指导该组中第三个合作伙伴Ingenza对微生物的工程改造。这三个合作伙伴将共同优化和扩大这一过程。所遵循的一般方法和所获得的具体结果都将引起生物技术专家的兴趣，因为它们将适用于开发使用可再生原料的许多其他散装和特种化学品的路线。这类以大宗化学品为基础的项目的成功将有助于促进英国成为生物基经济的领先者。该项目的成功还将在必要时推动其他化学品生产商参与工业生物技术和生物基工艺的开发。此外，将有广泛的利益，整个供应链与璐彩特的活动，从而提供更多的一般利益，整个英国经济。

We are beginning to see a shift in focus from of large-scale biotechnology away from biofuels (such as bioethanol and biobutanol) towards fine and bulk chemicals (e.g. succinic acid and propanediol) production. Methacrylic acid is the most widely used starting material to produce methylmethacrylate (MMA) for the manufacture of Perspex (also known as Lucite). MMA is a primary building block for the methacrylates industry and supports an extensive supply chain globally. All of this material is currently produced from petrochemical feedstocks. As a major player in the production of MMA (24% of total global production) one of the participating companies in this project, Lucite, is committed to developing a route based on renewable feedstocks. This project aims to engineer an industrial microbe to produce commercially viable amounts of a methacrylate precursor. The diversion of a large proportion of a microbe's resources to the generation of a product of no benefit to itself generally involves extensive realignment of its metabolic network. Scientists at the University of Cambridge will construct a computer model of the microbe's metabolism and use this in simulations to guide the engineering of the microbe by the third partner in this grouping, Ingenza. Together the three partners will optimise and scale-up the process. Both the general methodologies followed and specific results obtained will be of interest to biotechnologists, since they will be applicable to develop routes to many other bulk and speciality chemicals using renewable feedstocks. Success in a bulk chemical-based project of this type will help to promote the UK's aim to be at the leading edge of a Bio-based economy. Success in this project will also give impetus, where needed, to other chemical producers to engage in industrial biotechnology and the development of Bio-based processes. Furthermore, there will be extensive benefits throughout the supply chain associated with Lucite's activities, thus providing more general benefits across the UK economy.