Frontier Manufacturing: Scaling up synthetic biology

合成生物学有可能彻底改变我们制造大量消费品的方式，从材料和能源到食品和药品。为了实现这一影响，我们必须找到将实验室发现转化为工业生产过程的最佳方法。这里的挑战是从现有的工厂过渡到未来的工厂。今天，许多消费品都是使用合成化学技术从化石资源中制造的。未来，我们需要减少对石油产品的依赖，转向可再生资源。与此同时，合成生物学技术的出现可以快速定制用于制造目的的生物系统，这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在两个消费领域（治疗和化学品制造）的实际应用中合作，解决如何顺利完成这一过渡的问题。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。我们将需要新的生物传感器，以便能够在生产过程中进行监控，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，这些细胞可以耐受它们制造的高水平化合物，以及新的微反应器和/或在不需要整个细胞时使用酶的区室化策略。因为这种转变不会在一夜之间发生，我们需要开发出结合联合收割机生物和化学催化剂的中间体生产方法。这将需要对蛋白质和细胞毒性较小的溶剂，以及在化学物质存在下更坚固的蛋白质。为了开发经济高效的工艺（最小的能源和水的使用），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。首先是医疗保健，特别是药用化合物和治疗性蛋白质的生产。这些已经在很大程度上使用生物系统制造，但现有的过程既昂贵又复杂。此外，在未来，在需要时生产这些药物将更加有效（即时生产）。我们的目标是使用上述平台技术的组合，制造更简单，更具成本效益的即时生产系统：酶微反应器，专用细胞和生物传感器。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物（如生物质）的制造技术，并开发使用生物学和/或环境友好化学方法进行转化的新工艺。合成生物学从未在如此大的规模上进行过尝试。我们的挑战将是调整我们的部件、设备和系统，使其在这一水平上运行。总体结果将是新颖的，具有成本效益，节能和可持续的治疗和化学品路线。

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.