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

该项目是通过英国工程与物理科学研究委员会（ENG-EPSRC）牵头机构活动“化学、生物工程、环境和运输系统部门、土木、机械和制造创新部门以及电气、通信和网络系统部门提交合作提案特别指南”的机会获得的。该项目是与英国伦敦帝国理工学院合作进行的。非技术描述：大自然是强大的、可持续的、可生物降解材料的丰富来源。这些是很难在分子尺度上重建和重新设计的。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（GEMs）打开了大门。宝石的生产方式将与自然界中制造材料的方式相同：由不同类型的活细胞一起工作，每种细胞类型产生一种独特的聚合物。这种材料不经额外加工就可以使用。GEMs提供了制造新产品的途径，为现有行业（过滤、纺织、高级复合材料）提供可持续的替代品，或产生全新的行业（传感和响应材料）。技术描述：该项目将使用合成生物学方法开发第一代GEMs。它们将通过共同培养一组工程微生物来生产。这些微生物将产生细菌纳米纤维素（BC）纤维和融合到碳水化合物结合结构域的弹性蛋白样多肽（ELPs）。这两种都是重复的生物聚合物，每一种都具有工业上吸引人的特性。细菌制造的纳米纤维素非常纯净，具有生物相容性，并具有很高的机械负荷能力。酵母制造的elp对环境有反应，可以设计成随着盐、pH值或温度的变化而塌陷或延伸。该项目由四个目标组成，由英国和美国团队并行运行。这些都是为了解决实现GEMs的两个关键障碍：合理的蛋白质聚合物设计和优化高水平的蛋白质分泌。伦敦帝国理工学院的团队将构建并表征一个ELP文库，并建立分泌ELP的酵母和产生BC的细菌的初始共培养。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、核糖核酸-seq和计算建模）和定向进化来产生高分泌酵母菌株，并评估和优化它们在共培养条件下的性能。第五个目标将展示如何在DNA水平上通过工程将新特性编程到GEMs中。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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.