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

CBET-EPSRC - 生长工程材料 (GEM)：生物制造可调复合材料的合成联盟

• 批准号: EP/S032215/1
• 负责人: Thomas Ellis
• 金额: $ 56.27万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FS032215%2F1
• 关键词: CBET; EPSRC; Grown; Engineered; Materials

The 20th century saw unprecedented advances in the manufacture of materials, with chemical and mechanical engineering approaches enabling plastics, composites, aerogels and more. Now in the 21st century, our newfound abilities in biological engineering open the door to a new paradigm - Grown Engineered Materials (GEMs). Rather than blending together and chemically-modifying existing bulk materials ex situ, GEMs will be produced in vivo in the precise, sustainable way that materials are made by nature - with cells working together at the micro scale to grow different polymers in parallel that interact to form self-patterned composites. Using a synthetic biology approach, this breakthrough project will develop and demonstrate the first generation of GEMs, producing these by co-cultivating a set of engineered microbes that we have demonstrated can be grown together as a stable consortium. These material-producing microbes will produce GEMs made from nanocellulose fibres and elastin-like polypeptides (ELPs). These are both repetitive biopolymers that on their own have industrially-attractive properties; bacterial-made nanocellulose is exceptionally pure, biocompatible and possess a high mechanical load capability, while yeast-made ELPs are environment-responsive and can be designed to collapse or extend due to changes in levels of salt, pH or temperature. Having these two biomaterials co-synthesised together from growing engineered cells offers a novel route to making exciting new materials that offer properties beyond those of their constituent parts. This approach is inspired by nature, where we witness plants building impressive biomaterials from weaving cellulose into a mechanically-robust composites by incorporation of different polymers such as lignin. For example, the natural co-production of cellulose in composites with other biopolymers enhances the compressive strength of plant cell walls and also enables new characteristics to emerge.To demonstrate the paradigm of GEMs, our UK and US groups will work together in this project to synthesise and test different ELP designs for how the proteins interact within a growing nanocellulose fibre network. Alongside this we will study, engineer and optimise yeast strains so that these ELP proteins can be efficiently secreted into the growing material by engineered yeast cells that stably co-culture with the cellulose-producing bacteria. By the end of the project we expect to be able to grow high yields of ELP-cellulose composites in just a few days from only our mix of yeasts and bacteria and low-cost growth media. We will assess the material properties of these prototype GEMs and then use synthetic biology tools, such as optogenetics and pattern formation to control how, where and when the composites are made at the micro-scale. This ambitious interdisciplinary research project will utilise many state-of-the-art approaches to biological engineering that our two groups have international expertise in. From synthetic protein polymer design, strain optimisation and synthetic biology genetic control, right through to systems biology, transcriptomics, machine learning and biomaterial characterisation. We plan to produce a range of ELP-cellulose composite materials that are genetically-tunable, so that changes in the way DNA is written in the microbial cells can predictably lead to changes in the materials and their properties. Our aim is to realise the paradigm of GEMs and provide the blueprint, engineered strains and synthetic biology toolkit for others to utilise this approach in the future.

20世纪见证了材料制造的空前进步，化学和机械工程方法使塑料、复合材料、气凝胶等成为可能。现在在21世纪，我们在生物工程方面新发现的能力打开了一扇通往新范式的大门——生长工程材料（GEMs）。GEMs不是混合在一起，对现有的块状材料进行化学修饰，而是以精确、可持续的方式在体内生产，就像材料是由自然产生的一样——细胞在微观尺度上协同工作，平行生长不同的聚合物，相互作用形成自图案复合材料。利用合成生物学的方法，这个突破性的项目将开发和展示第一代GEMs，通过共同培养一组工程微生物来生产这些GEMs，我们已经证明这些微生物可以作为一个稳定的联合体一起生长。这些生产材料的微生物将生产由纳米纤维素纤维和弹性蛋白样多肽（elp）制成的GEMs。这些都是重复的生物聚合物，它们本身具有工业上的吸引力；细菌制造的纳米纤维素非常纯净，具有生物相容性，具有很高的机械负荷能力，而酵母制造的elp对环境敏感，可以设计成由于盐、pH或温度水平的变化而坍塌或延伸。将这两种生物材料从生长的工程细胞中合成在一起，为制造令人兴奋的新材料提供了一条新途径，这种新材料提供了超越其组成部分的性能。这种方法的灵感来自大自然，我们看到植物通过将不同的聚合物（如木质素）结合在一起，将纤维素编织成机械坚固的复合材料，从而制造出令人印象深刻的生物材料。例如，复合材料中纤维素与其他生物聚合物的天然协同生产增强了植物细胞壁的抗压强度，也使新的特性得以出现。为了展示GEMs的范例，我们的英国和美国团队将在这个项目中合作，合成和测试不同的ELP设计，以了解蛋白质如何在不断增长的纳米纤维素纤维网络中相互作用。除此之外，我们还将研究、设计和优化酵母菌株，以便这些ELP蛋白可以通过与生产纤维素的细菌稳定共培养的工程酵母细胞有效地分泌到生长材料中。到项目结束时，我们预计仅用酵母和细菌的混合以及低成本的生长介质，就能在几天内培养出高产量的elp -纤维素复合材料。我们将评估这些原型GEMs的材料特性，然后使用合成生物学工具，如光遗传学和模式形成来控制在微观尺度上制造复合材料的方式、地点和时间。这个雄心勃勃的跨学科研究项目将利用我们两个团队在生物工程方面拥有的国际专业知识。从合成蛋白聚合物设计、菌株优化和合成生物学遗传控制，一直到系统生物学、转录组学、机器学习和生物材料表征。我们计划生产一系列基因可调的elp -纤维素复合材料，这样微生物细胞中DNA写入方式的变化就可以预测地导致材料及其性能的变化。我们的目标是实现GEMs的范例，并为其他人在未来利用这种方法提供蓝图，工程菌株和合成生物学工具包。

项目成果

Self-healing through adhesion.

通过粘附进行自我修复。

• DOI: 10.1038/s41589-021-00946-9
• 发表时间: 2022
• 期刊: Nature chemical biology
• 影响因子: 14.8
• 作者: Caro-Astorga J