Collaborative Proposal: Exploiting synthetic GPCRs and mating factors as extracellular sensors for substrate-dependent assembly of complex cellulosomes

阻碍更广泛地将生物质用于能源和化学生产的主要障碍是缺乏一种低成本的技术来克服这些材料的顽固性。纤维素体是自组装的多酶复合物，存在于许多厌氧微生物中，对生物质解聚非常有效。这组研究人员已经成功地开发了一个合成酵母联合体，展示了用于生物燃料生产的功能性纤维素。然而，考虑到联合体中不同成员的复杂性，设计细胞与细胞之间的协调是维持所需整体功能的关键。他们在这个项目中的目标是设计合成的细胞外传感器，该传感器可用于调节酶和接头支架蛋白的分泌，这些酶和支架蛋白以依赖底物的方式参与适当复杂纤维素结构的组装。这项研究具有重要的科学意义，因为它将为细胞外传感器的设计提供一个总体框架，这对其他生物处理或生物医学应用很重要。此外，参与这项研究的研究生将获得一个综合的视角，了解生物化学、现代遗传学和过程工程之间的重要接口和协同作用，以解决我们社会的一个重要问题。

1263719/1263768/1263799Chen/Robinson/Da Silva The primary obstacle impeding the more widespread use of biomass for energy and chemical production is the absence of a low-cost technology for overcoming the recalcitrance of these materials. Cellulosomes are self-assembled multi-enzyme complexes found in many anaerobic microorganisms that are highly efficient for biomass depolymerization. The group of investigators have successfully developed a synthetic yeast consortium displaying a functional cellulosome for biofuel production. However, given the complexity of the different members involved in the consortium, engineering cell to cell coordination is the key in maintaining the required overall functionality. Their goal in this project is to design synthetic extracellular sensors that can be used to regulate the secretion of enzymes and adaptor scaffoldins involved in the assembly of the appropriate complex cellulosome structure in a substrate-dependent manner. The proposed research is scientifically significant because it will provide a general framework for the design of extracellular sensors that are important for other bioprocessing or biomedical applications. Moreover, graduate students participating in this research will gain an integrated perspective of the important interfaces and synergies connecting biochemistry, modern genetics, and process engineering to solve an important problem of our society.