Development of whole cell biocatalysts for biomass and plastic degradation

当今社会存在两大挑战：1)我们如何以更可持续的方式消费；2)我们如何将环境污染降到最低。由于现代社会严重依赖有限的石油储备来供应燃料和化学品，因此，将我们的依赖从这些不可持续的石油原料转向可再生原料是发展低碳生物经济的关键因素。如果能够开发出有效增值的方法，从生物质原料中提取的木质素作为芳香族化合物的可再生来源具有很大的潜力。与此同时，不可生物降解材料（如塑料）造成的环境污染，既对人类有负面影响，需要解决，但如果储存的代谢能量能够释放出来，它本身也为工程微生物的生长提供了另一种碳来源。合成生物学和代谢工程提供了潜在的协同作用，使细胞工厂的发展具有新的生物合成途径，从这些生物质和塑料来源中获得有价值的化学物质。然而，由于缺乏能够筛选大型遗传变异文库和与生物生产相关的代谢负担的高通量方法，途径设计和优化是一个主要瓶颈。基因编码的生物传感器可以提供一种解决方案，通过将目标代谢物浓度转导为可检测的信号，提供高通量表型读出并允许动态途径调节。生物传感器在木质素降解、转化和增值的有效生物催化过程的发现和工程中的发展和应用，为可持续和经济上可行的生物炼制铺平了道路。这位曼彻斯特生物技术研究所的博士生将由Neil Dixon博士、Nigel Scrutton教授和Antony Green博士共同指导，并将专注于利用基因编码的生物传感器开发用于生物质和塑料降解的全细胞生物催化剂。具体来说，该计划将致力于发现、优化和应用微生物转运体，负责整个生物催化剂的底物和产品的进出口。学生将在生物技术、微生物基因表达调控、合成生物学工具和原理的使用、生物催化、定向进化、微生物发酵、分子生物学和生物分析方法（如GC-MS）等广泛方面接受培训。本项目适合对未来生物技术、生物催化和生物加工领域感兴趣的个人。该博士项目将通过提供各种方法的培训来开发新的工作方式，即这将包括分子和微生物学，数据处理和统计分析的实验室技能，以及FACS等分析流程方法。这将为博士生提供使用和应用定量数据驱动方法的能力，以更全面地理解生物学问题。除了培训之外，研究项目的目标/产出本身将开发新的工作方式，因为它们将为高价值精细化学品的高产工艺的产生和对细菌细胞运输的见解提供创新的工具和技术方法。

Two major societal challenges exist today i) how can we consumable more sustainably and ii) how can we minimise environmental contamination. As modern society is hugely dependent on finite oil reserves for the supply of fuels and chemicals, moving our dependence away from these unsustainable oil-based feedstocks to renewable ones is therefore a critical factor towards the development of a low carbon bioeconomy. Lignin derived from biomass feedstocks offers great potential as a renewable source of aromatic compounds if methods for its effective valorization can be developed. In parallel environmental contamination with non-biodegradable material such as plastic, are both a negative human impact that needs to be resolved but in itself offers an alternative source of carbon, for growth of engineered microbes, if the stored metabolic energy can be released.Synthetic biology and metabolic engineering offer the potential to synergistically enable the development of cell factories with novel biosynthetic routes to valuable chemicals from both of these biomass and plastic sources. Pathway design and optimization is however a major bottleneck due to the lack of high-throughput methods capable of screening large libraries of genetic variants and the metabolic burden associated with bioproduction. Genetically encoded biosensors can provide a solution by transducing the target metabolite concentration into detectable signals to provide high-throughput phenotypic read-outs and allow dynamic pathway regulation. The development and application of biosensors in the discovery and engineering of efficient biocatalytic processes for the degradation, conversion and valorization of lignin is paving the way towards a sustainable and economically viable biorefinery.The PhD student based in Manchester Institute of Biotechnology will be co-supervised by Dr. Neil Dixon, and Prof Nigel Scrutton, and Dr Antony Green, and will be focused on the development of whole cell biocatalysts for biomass and plastic degradation using genetically encoded biosensors. Specifically the programme will aim to discover, optimise and apply microbial transporter, responsible for the import and export of substrates and products from whole biocatalysts. The student will be trained in broad aspects of biotechnology, microbial gene expression regulation, use of synthetic biology tools and principles, biocatalysis, directed evolution, microbial fermentation, molecular biology and bio-analytical methods such GC-MS. This project would suit individuals interested in future careers in biotechnology, biocatalysis and bioprocessing.This PhD project will exploit new ways of working by providing training in a variety of approaches namely this will include lab based skills in molecular and microbiology, data processing and statistical analysis, and analytical flow methods such FACS. This will provide the PhD student with the ability to use and apply quantitative data-driven approaches to more fully understand biological questions. In addition to the training the research project goals/outputs in themselves will exploit new ways of working, as they will provide innovative tools and technological approaches for the generation of highly productive processes for high-value fine chemicals and insights into bacterial cell transport.