Du Wei, Burbano Patricia Caicedo, Hellingwerf Klaas J, Branco Dos Santos Filipe
Molecular Microbial Physiology Group, Swammerdam Institute for Life Sciences, Faculty of Sciences, University of Amsterdam, Amsterdam, The Netherlands.
Adv Exp Med Biol. 2018;1080:3-26. doi: 10.1007/978-981-13-0854-3_1.
Cyanobacterial direct conversion of CO to several commodity chemicals has been recognized as a potential contributor to support the much-needed sustainable development of human societies. However, the feasibility of this "green conversion" hinders on our ability to overcome the hurdles presented by the natural evolvability of microbes. The latter may result in the genetic instability of engineered cyanobacterial strains leading to impaired productivity. This challenge is general to any "cell factory" approach in which the cells grow for multiple generations, and based on several studies carried out in different microbial hosts, we could identify that three distinct strategies have been proposed to tackle it. These are (1) to reduce microbial evolvability by decreasing the native mutation rate, (2) to align product formation with cell growth/fitness, and, paradoxically, (3) to efficiently reallocate cellular resources to product formation by uncoupling it from growth. The implementation of either of these strategies requires an advanced synthetic biology toolkit. Here, we review the existing methods available for cyanobacteria and identify areas of focus in which specific developments are still needed. Furthermore, we discuss how potentially stabilizing strategies may be used in combination leading to further increases of productivity while ensuring the stability of the cyanobacterial-based direct conversion process.
蓝细菌将一氧化碳直接转化为多种商品化学品已被认为是支持人类社会急需的可持续发展的潜在贡献者。然而，这种“绿色转化”的可行性取决于我们克服微生物自然进化能力所带来障碍的能力。后者可能导致工程蓝细菌菌株的遗传不稳定，从而导致生产力受损。这一挑战对于任何细胞生长多代的“细胞工厂”方法来说都是普遍存在的，基于在不同微生物宿主中进行的多项研究，我们可以确定已经提出了三种不同的策略来应对这一挑战。这些策略是：（1）通过降低天然突变率来降低微生物的进化能力；（2）使产物形成与细胞生长/适应性保持一致；以及自相矛盾的是，（3）通过将产物形成与生长解偶联来有效地将细胞资源重新分配到产物形成中。实施这些策略中的任何一种都需要先进的合成生物学工具包。在这里，我们回顾了现有的蓝细菌可用方法，并确定了仍需要具体发展的重点领域。此外，我们讨论了如何将潜在的稳定策略结合使用，以在确保基于蓝细菌的直接转化过程稳定性的同时进一步提高生产力。
