CBET-EPSRC: Grown Engineered Materials (GEMs): synthetic consortia for biomanufacturing tunable composites

该项目是通过“化学、生物工程、环境和运输系统司、土木工程、机械和制造创新司以及电气、通信和网络系统司--英国工程和物理科学研究理事会(ENG-EPSRC)牵头机构活动下提交合作建议书的特别指导方针”授予的。该项目是与英国帝国理工学院合作完成的。非技术描述：大自然是坚固、可持续和可生物降解材料的丰富来源。这些都很难在分子水平上重新创造和重新设计。合成生物学的最新成就为一种新的制造范式--生长工程材料(GEM)打开了大门。宝石的产生方式与材料在自然界中的形成方式相同：由不同类型的活细胞共同工作，每种细胞类型产生一种独特的聚合物。这种材料只需很少的额外加工即可使用。GEM提供了一条制造新产品的途径，为现有行业(过滤、纺织、先进复合材料)提供了可持续的替代方案，或产生了全新的行业(传感和响应材料)。技术描述：该项目将使用合成生物学方法来开发第一代GEM。这些将通过共同培养一组工程微生物来产生。这些微生物将产生融合到碳水化合物结合域的细菌纳米纤维素(BC)纤维和弹性蛋白样多肽(ELP)。这两种生物聚合物都是可重复的生物聚合物，每一种都具有独特的工业吸引力。细菌制造的纳米纤维素非常纯净，具有生物相容性，并具有高机械负荷能力。酵母制成的ELP是环境敏感型的，可以设计成因盐水平、pH或温度的变化而坍塌或伸展。该项目由四个目标组成，由英国和美国的团队并行运行。这些都是为了解决实现宝石的两个关键障碍：合理的蛋白质聚合物设计和优化蛋白质的高水平分泌。伦敦帝国理工学院的研究小组将构建和鉴定ELP文库，并建立ELP分泌酵母和BC产生细菌的初步共培养。加州大学河滨分校的研究小组将应用系统生物学(亚细胞RNA-seq、Ribo-seq和计算建模)和定向进化来产生高分泌酵母菌株，以及评估和优化它们在共培养条件下的表现。第五个目标将展示如何在DNA水平上通过工程学将新特性编程到宝石中。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

This project was awarded through the "Special Guidelines for Submitting Collaborative Proposals under the Division of Chemical, Bioengineering, Environmental, and Transport Systems, the Division of Civil, Mechanical, and Manufacturing Innovation, and the Division of Electrical, Communications, and Cyber Systems - the UK Engineering and Physical Sciences Research Council (ENG-EPSRC) Lead Agency Activity" opportunity. This project is performed in collaboration with Imperial College, London, an institution in the UK.Nontechnical description: Nature is a rich source of strong, sustainable, and biodegradable materials. These are difficult to recreate and re-engineer at the molecular scale. Recent achievements in synthetic biology open the door to a new manufacturing paradigm, Grown Engineered Materials (GEMs). GEMs will be produced in the same way that materials are made in nature: by different types of living cells working together, with each cell type producing a unique polymer. This material can be used with little additional processing. GEMs offer a route to make new products, offer sustainable alternatives to existing industries (filtration, textiles, advanced composites) or yield entirely new sectors (sensing and responsive materials).Technical description: This project will use synthetic biology approaches to develop the first generation of GEMs. These will be produced by co-cultivating a set of engineered microbes. These microbes will produce Bacterial nanoCellulose (BC) fibers and Elastin-Like Polypeptides (ELPs) fused to carbohydrate-binding domains. These are both repetitive biopolymers, and each has industrially-attractive properties on its own. Bacterial-made nanocellulose is exceptionally pure, biocompatible, and possesses a high mechanical load capability. Yeast-made ELPs are environment-responsive and can be designed to collapse or extend due to changes in levels of salt, pH, or temperature. The project consists of four objectives to be run in parallel by the UK and US teams. These are designed to tackle the two key hurdles to realizing GEMs: rational protein polymer design and optimizing high-level secretion of proteins. The team at Imperial College, London will construct and characterize an ELP library, as well as establish initial co-culturing of ELP secreting yeast and BC producing bacteria. The team at University of California, Riverside will apply systems biology (subcellular RNA-seq, Ribo-seq, and computational modeling) and directed evolution to generate hypersecreting yeast strains, as well as assess and optimize their performance under co-culturing conditions. A fifth objective will showcase how novel properties can be programmed into GEMs by engineering at the DNA level.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.