微生物中一碳代谢网络构建的进展与挑战

Developing C_(1)-based metabolic network in methylotrophy for biotransformation

利用来源广、价格低、易制备且储量丰富的一碳化合物作为底物,通过构建甲基营养型细胞工厂,生物合成多种高附加值化学品,不仅可以促进一碳资源的洁净利用,同时可以缓解能源短缺、环境污染等问题。因此,深入了解甲基营养型微生物(天然型和合成型)的一碳代谢网络,是高效利用一碳化合物进行生物炼制的关键。本文综述了多种一碳化合物(甲烷、甲醇、甲酸和二氧化碳)生物炼制的研究进展,主要包括两个部分:(1)甲基营养型微生物(天然型和合成型)的关键代谢酶及多种代谢网络;(2)基于多种甲基营养型微生物进行生物合成的研究现状。文章最后讨论了一碳化合物作为底物进行生物转化所面临的主要瓶颈,并据此提供可行的研究策略,以期推动一碳化合物作为原材料进行生物炼制的工业化进程。

One carbon(C_(1))substrates have generated increasing attention as abundantly available feedstock for biotransformation to produce biofuels and valuable chemicals.Especially,these bioproducts are not only promoting the economic development,but also meet the societal needs for clean energy and environmental protection.Microbial cell factories(MCF)that efficiently convert raw materials to useful chemicals are highly desirable for C_(1)based biomanufacturing.Furthermore,more and more attention is being paid to study how the native and synthetic methylotrophic MCFs are capable of utilizing C_(1)compounds including methane,methanol,formic acid and carbon dioxide(CO_(2))as raw materials for biosynthesis.Native methylotrophs have multiple pathways for C_(1)utilization so that they can grow with methanol or formate as the sole carbon and energy source.Engineering synthetic methylotrophs are based on available metabolic knowledge and advanced genome engineering tools to modify the platform microorganisms.Hence,it is the key to explore the C_(1)-based metabolic networks of methylotrophy in depth for constructing highly effective methylotrophic cell factory to convert C_(1)substrates.In this review,we firstly summarize in detail key natural pathways for C_(1)-substrate assimilation and bioproducts produced by native methylotrophs.Then we introduce synthetic methylotrophs and major chemical products derived through engineering Escherichia coli,Corynebacterium glutamicum and Saccharomyces cerevisiae.In the field of synthetic methylotrophs,many studies focus on utilizing methanol or CO_(2)as the sole carbon source and energy source to construct the MCFs for bio-transformation.In the end,we discuss the barriers and challenges for developing robust methylotrophic cell factory to convert C_(1)substrates,and highlight strategies for commercializing the biotransformation of C_(1)based substrates.