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，材料制造方面取得了前所未有的进步，化学和机械工程方法可以实现塑料，复合材料，气凝胶等。现在，在21世纪，我们在生物工程领域的新发现的能力为新的范式 - 生长工程材料（GEMS）打开了大门。与与化学改造的现有散装材料相混合在一起，将以精确，可持续的方式在体内生产材料，使材料是由自然制成的 - 细胞在微型尺度上共同工作，以并行生长不同的聚合物，以形成自形的复合材料。使用合成生物学方法，该突破性项目将开发并证明第一代宝石，通过共同培养一组我们已经证明的工程微生物来生产这些宝石，可以作为一个稳定的财团一起生长。这些产生物质的微生物将产生由纳米纤维素纤维和弹性蛋白样多肽（ELP）制成的宝石。这些都是重复的生物聚合物，它们本身具有工业吸引的特性。细菌制造的纳米纤维素异常纯净，具有生物相容性并且具有高机械负载能力，而酵母菌的ELP具有环境反应性，并且由于盐，pH或温度水平的变化而可设计为塌陷或延伸。从不断增长的工程细胞中将这两种生物材料共同合成共同合成，提供了一种新型的途径，以制造令人兴奋的新材料，以提供超出其组成部分的特性。这种方法的灵感来自自然，我们目睹植物通过掺入诸如木质素等不同聚合物（例如木质素），从编织纤维素从编织纤维素织成机械燃料的复合材料。例如，与其他生物聚合物在复合材料中纤维素的自然共生产增强了植物细胞壁的抗压强度，还可以使新的特征出现。为了展示宝石的范式，我们的英国和我们团体将在该项目中共同努力，以合成和测试蛋白质在生长的Nananocellose enanocellose网络中相互作用的不同ELP设计。除此之外，我们将研究和优化酵母菌菌株，以便通过工程酵母细胞有效地分泌这些ELP蛋白，这些细胞可以稳定地与产生纤维素的细菌共同培养。到该项目结束时，我们希望能够在短短几天内从酵母，细菌和低成本生长培养基中造成高产量的ELP-纤维素复合材料。我们将评估这些原型宝石的材料特性，然后使用合成生物学工具，例如光遗传学和图案形成，以控制在微观尺度上制作复合材料的方式，何时何地。这个雄心勃勃的跨学科研究项目将利用许多最先进的生物工程方法，我们的两个小组都具有国际专业知识。从合成蛋白聚合物设计，菌株优化和合成生物学遗传控制，直到系统生物学，转录，机器学习和机器学习和生物材料表征。我们计划生产一系列可在遗传上触发的ELP-纤维素复合材料，以便可以预见的是在微生物细胞中写入DNA的方式可以预测导致材料及其特性的变化。我们的目的是实现宝石的范式，并提供蓝图，工程菌株和合成生物学工具包，以便其他人在将来利用这种方法。

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