Klein Vivien Jessica, Irla Marta, Gil López Marina, Brautaset Trygve, Fernandes Brito Luciana
Department of Biotechnology and Food Science, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
Microorganisms. 2022 Jan 20;10(2):220. doi: 10.3390/microorganisms10020220.
Formaldehyde metabolism is prevalent in all organisms, where the accumulation of formaldehyde can be prevented through the activity of dissimilation pathways. Furthermore, formaldehyde assimilatory pathways play a fundamental role in many methylotrophs, which are microorganisms able to build biomass and obtain energy from single- and multicarbon compounds with no carbon-carbon bonds. Here, we describe how formaldehyde is formed in the environment, the mechanisms of its toxicity to the cells, and the cell's strategies to circumvent it. While their importance is unquestionable for cell survival in formaldehyde rich environments, we present examples of how the modification of native formaldehyde dissimilation pathways in nonmethylotrophic bacteria can be applied to redirect carbon flux toward heterologous, synthetic formaldehyde assimilation pathways introduced into their metabolism. Attempts to engineer methylotrophy into nonmethylotrophic hosts have gained interest in the past decade, with only limited successes leading to the creation of autonomous synthetic methylotrophy. Here, we discuss how native formaldehyde assimilation pathways can additionally be employed as a premise to achieving synthetic methylotrophy. Lastly, we discuss how emerging knowledge on regulation of formaldehyde metabolism can contribute to creating synthetic regulatory circuits applied in metabolic engineering strategies.
甲醛代谢在所有生物体中都普遍存在，通过异化途径的活性可以防止甲醛的积累。此外，甲醛同化途径在许多甲基营养菌中起着重要作用，这些甲基营养菌是能够利用不含碳 - 碳键的单碳和多碳化合物构建生物质并获取能量的微生物。在这里，我们描述了环境中甲醛是如何形成的，其对细胞的毒性机制，以及细胞规避它的策略。虽然它们对于在富含甲醛的环境中细胞存活的重要性是毋庸置疑的，但我们给出了一些例子，说明如何通过改造非甲基营养菌中的天然甲醛异化途径，将碳通量导向引入其代谢的异源合成甲醛同化途径。在过去十年中，将甲基营养能力工程化到非甲基营养宿主中的尝试引起了人们的兴趣，但取得的成功有限，仅导致了自主合成甲基营养的产生。在这里，我们讨论了如何将天然甲醛同化途径额外用作实现合成甲基营养的前提。最后，我们讨论了关于甲醛代谢调控的新知识如何有助于创建应用于代谢工程策略的合成调控回路。
