Reducing CO2 emissions during chemical production through the Synthetic Biology of complex microbial communities

社会面临的最大挑战之一是未来从非石化资源中可持续地生产化学品和燃料，同时减少温室气体排放。使用丰富的和可再生的木质纤维素材料，可以物理预处理，以产生纤维素和C5馏分作为原料，使化学品和燃料可以是非常有价值的，如果该过程是有效的，并尽量减少CO2 production.This奖学金将被链接到最近资助的BBSRC项目，是欧洲EraCoBiotech计划之间的诺丁汉，图卢兹，慕尼黑和赫罗纳大学的一部分。其目的是设计合成微生物群落，以生产增值产品正丁醇，可用作平台化学品或生物燃料。诺丁汉负责工程化的梭菌carboxidivorans，正丁醇生产产乙酸菌。模式产乙酸菌，如自产乙醇梭菌（Clostridium autoethanogenum）（LanzaTech公司的底盘），仅产生C2产物乙酸盐和乙醇。C.另一方面，carboxidivorans（Synata Bio的底盘）也生产丁酸盐、丁醇和己醇，这些都是更有价值的C4和C6化学品。例如，己醇是一种比乙醇具有更高能量含量的高碳醇。当与煤油和柴油混合时，它有可能用作航空燃料和运输燃料。它还用于制药和化妆品香料工业、纺织工业、洗涤剂、杀虫剂、皮革助剂和渔业等。2016年全球己醇市场规模估计超过11亿美元，到2024年将增长4%以上。然而，从未证明过carboxidivorans，排除了有效的代谢工程策略。位于诺丁汉的BBSRC/EPSRC合成生物学研究中心（SBRC）的科学家们现在已经克服了这一障碍。因此，在这个项目中，您将与我们的欧洲合作伙伴合作，优化C中有效基因组编辑所需的关键步骤。这些技术包括CRISPR/Cas9、CRISPRi、TARGET-AID和基于转座子的TraDIS技术。一旦到位，您将使用这些开发成果来提高己醇的生产，使用CRISPR技术来消除竞争反应（例如导致乙酸，丁酸和乳酸的反应）以及优化天然基因的表达。受竞争途径影响的突变体将进行表型表征和组学分析（在图卢兹大学），结果用于改进SBRC基因组规模模型。最终的菌株可能会被纳入设想的合成社区，以制造己醇。学生将完全融入欧洲项目，参加在德国（慕尼黑），法国（图卢兹）和西班牙（赫罗纳）的4所大学轮流举行的六个月的项目会议。也可以有时间限制地借调到合作大学。最终，所取得的发展将带来新的、可持续的工业流程，为减少二氧化碳排放做出真实的贡献。

One of the greatest challenges facing society is the future sustainable production of chemicals and fuels from non-petrochemical resources while at the same time reducing greenhouse gas emissions. The use of abundant and renewable lignocellulosic materials, that can be physically pretreated to yield both cellulosic and C5 fractions as feed stocks to make chemicals and fuels can be highly valuable if the process is efficient and minimises CO2 production.This studentship will be linked to a recently funded BBSRC project that is part of the European EraCoBiotech programme between the Universities of Nottingham, Toulouse, Munich and Girona. The aim is to engineer synthetic microbial consortium to produce to a value added product, n-butanol, that can be used both as a platform chemical or a biofuel. Nottingham is responsible for the engineering of Clostridium carboxidivorans, n-butanol producing acetogen. Model acetogens, such as Clostridium autoethanogenum (chassis of the company LanzaTech), only make the C2 products acetate and ethanol. C. carboxidivorans (chassis of Synata Bio) on the other hand, also makes butyrate, butanol and hexanol, more valuable C4 and C6 chemicals. Hexanol, for instance, is a higher carbon alcohol with a higher energy content than ethanol. It has potential for use as an aviation fuel and as a transportation fuel when blended with kerosene and diesel. It is also used in the pharmaceutical and cosmetic perfumes industry, textile industry, in detergents, in pesticides, agent in the leather and as a fishing industry, among others.The global hexanol market size was estimated at over USD 1.1 billion in 2016 and will exhibit growth of more than 4% up to 2024.Until now, gene transfer into this C. carboxidivorans had never been demonstrated, precluding effective metabolic engineering strategies. Scientists at the BBSRC/EPSRC Synthetic Biology Research Centre (SBRC) at Nottingham have now overcome this impediment. In this project you will, therefore, work with our European partners in the optimisation of the key steps required for effective genome editing in C. carboxidivorans, including CRISPR/Cas9, CRISPRi, TARGET-AID and transposon-based TraDIS technology. Once in place you will use these developments to enhance hexanol production using CRISPR technologies to eliminate competing reactions (such as those leading to acetate, butyrate and lactate) as well as optimising expression of native genes. Mutants affected in competing pathways will be subjected to phenotypic characterisation and omics analyses (at the University of Toulouse), and results used to improve an SBRC Genome Scale Model. The final strain may be incorporated into the envisaged synthetic community to make hexanol.The student will become fully integrated into the European project, attending the six monthly project meetings to be held in rotation at the 4 Universities, in Germany (Munich), France (Toulouse) and Spain (Girona). Time limited secondments to partner Universities may also be possible.Ultimately, the developments made will lead to new, sustainable industrial processes that could make a real contribution to reducing CO2 emissions.