Frontier Manufacturing: Scaling up synthetic biology

前沿制造：扩大合成生物学规模

• 批准号: EP/K038648/1
• 负责人: Donal Bradley
• 金额: $ 657.3万
• 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: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FK038648%2F1
• 关键词: Frontier; Manufacturing; Scaling; up; synthetic

Synthetic biology has the potential to revolutionise the way we make a host of consumer products from materials and energy to food and medicine. In order for this impact to be realised, we must find the best way to translate laboratory discoveries into operating industrial production processes. The challenge here is to transition from existing factories into the factories of the future. Today many consumer products are made from fossil resources using synthetic chemistry techniques. In the future we will need to reduce our dependence on petroleum products and move to renewable resources. At the same time, the advent of synthetic biology techniques for rapidly tailoring biological systems for manufacturing purposes will allow us to transition away from synthetic chemistry and into more environmentally friendly production mechanisms using cells. We will tackle the question of how to undergo this transition smoothly by working with our industrial partners on real-world applications in two consumer areas (therapeutics and chemicals manufacturing). Developing these future biofactories will require the invention of some new generalised technologies to underpin the new manufacturing processes. We will need new biologically based sensors in order to be able to monitor the production processes as they occur to ensure the product quality (and to allow us to intervene if necessary). We will also need new, more robust production cells that can tolerate the high levels of compounds they make and new microreactors and/or compartmentalisation strategies for using enzymes when whole cells are not required. Because the transition will not happen overnight, we will need to develop intermediate production methods that combine biological and chemical catalysts. This will require solvents that are less toxic to proteins and cells and proteins that are engineered to be more robust in the presence of chemicals. In order to develop processes that are economical and efficient (minimal energy and water usage), we will create computer models to compare alternatives. The most promising processes will be implemented in the factories of our industrial partners. We have chosen two challenge areas in which to test our new technologies. The first is healthcare, specifically the manufacture of medicinal compounds and therapeutic proteins. These are already largely made using biological systems, but the existing processes are expensive and complicated. Also, in the future, it would be more efficient to make these medicines as and when they are needed (point-of-care manufacture). Our goals are to make simpler, more cost effective, point-of-care manufacturing systems using a combination of the above mentioned platform technologies: enzyme microreactors, specialised cells, and biosensors. Our second target is to produce bulk chemicals without the need for petroleum inputs. This will require us to adjust our manufacturing techniques for renewable inputs (such as biomass) and to develop new processes that use biology and/or environmentally friendly chemistry to do the conversions. Synthetic biology has never been attempted on such a large scale. Our challenge will be to adapt our parts, devices, and systems to operate at this level. The overall outcome will be novel, cost effective, energy efficient, and sustainable routes to therapeutics and chemicals.

合成生物学有潜力彻底改变我们制造从材料和能源到食品和药品的大量消费品的方式。为了实现这种影响，我们必须找到将实验室发现转化为工业生产流程的最佳方法。这里的挑战是从现有工厂过渡到未来工厂。如今，许多消费品都是利用合成化学技术由化石资源制成的。未来我们需要减少对石油产品的依赖并转向可再生资源。与此同时，用于快速定制用于制造目的的生物系统的合成生物学技术的出现将使我们能够从合成化学过渡到使用细胞的更环保的生产机制。我们将通过与我们的工业合作伙伴合作，在两个消费领域（治疗和化学品制造）的实际应用中解决如何顺利过渡的问题。开发这些未来的生物工厂将需要发明一些新的通用技术来支持新的制造工艺。我们将需要新的基于生物的传感器，以便能够监控生产过程，以确保产品质量（并允许我们在必要时进行干预）。我们还需要新的、更强大的生产细胞，能够耐受它们产生的高水平化合物，以及新的微反应器和/或在不需要全细胞时使用酶的区室化策略。由于这种转变不会在一夜之间发生，我们需要开发结合生物和化学催化剂的中间生产方法。这需要对蛋白质和细胞毒性较小的溶剂，以及经过改造的蛋白质在化学物质存在下更稳定。为了开发经济高效的工艺（最少的能源和水的使用），我们将创建计算机模型来比较替代方案。最有前途的工艺将在我们的工业合作伙伴的工厂中实施。我们选择了两个挑战领域来测试我们的新技术。第一个是医疗保健，特别是药用化合物和治疗性蛋白质的制造。这些已经主要使用生物系统制造，但现有工艺昂贵且复杂。此外，将来，在需要时生产这些药物（即时制造）将会更加高效。我们的目标是结合使用上述平台技术：酶微反应器、专用细胞和生物传感器，制造更简单、更具成本效益的即时制造系统。我们的第二个目标是在不需要石油投入的情况下生产大宗化学品。这将要求我们调整可再生投入（例如生物质）的制造技术，并开发使用生物学和/或环保化学来进行转换的新工艺。合成生物学从未进行过如此大规模的尝试。我们的挑战将是调整我们的零件、设备和系统以在这个级别上运行。总体成果将是新颖、具有成本效益、节能且可持续的治疗和化学品途径。

项目成果

Sculpting and fusing biomimetic vesicle networks using optical tweezers.

使用光镊雕刻和融合仿生囊泡网络。

• DOI: http://dx.10.1038/s41467-018-04282-w
• 发表时间: 2018
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Bolognesi G

A systematic analysis of the expression of the anti-HIV VRC01 antibody in Pichia pastoris through signal peptide optimization.

通过信号肽优化系统分析抗HIV VRC01抗体在毕赤酵母中的表达。

• DOI: http://dx.10.1016/j.pep.2018.03.013
• 发表时间: 2018
• 期刊: Protein expression and purification
• 影响因子: 1.6
• 作者: Aw R

Cell free protein synthesis: a viable option for stratified medicines manufacturing?

无细胞蛋白质合成：分层药物制造的可行选择？

• DOI: 10.1016/j.coche.2017.10.003
• 发表时间: 2017-11-01
• 期刊: Current opinion in chemical engineering
• 作者: O. Ogonah;K. Polizzi;D. Bracewell
• 通讯作者: D. Bracewell

Biosensor-assisted engineering of a high-yield Pichia pastoris cell-free protein synthesis platform.

高产毕赤酵母无细胞蛋白质合成平台的生物传感器辅助工程。

• DOI: http://dx.10.1002/bit.26901
• 发表时间: 2019
• 期刊: Biotechnology and bioengineering
• 影响因子: 3.8
• 作者: Aw R

Thermally robust solvent-free biofluids of M13 bacteriophage engineered for high compatibility with anhydrous ionic liquids.

M13 噬菌体的耐热无溶剂生物流体，经过精心设计，与无水离子液体具有高相容性。

• DOI: http://dx.10.1039/c9cc04909f
• 发表时间: 2019
• 期刊: Chemical communications (Cambridge, England)
• 作者: Brogan APS