Synthetic or natural? Metabolic engineering for assimilation and valorization of methanol

Single carbon (C1) substrates such as methanol are gaining increasing attention as cost-effective and environmentally friendly microbial feedstocks. Recent impressive metabolic engineering efforts to import C1 catabolic pathways into the non-methylotrophic bacterium Escherichia coli have led to synthetic strains growing on methanol as the sole carbon source. However, the growth rate and product yield in these strains remain inferior to native methylotrophs. Meanwhile, an ever-expanding genetic engineering toolbox is increasing the tractability of native C1 utilizers, raising the question of whether it is best to use an engineered strain or a native host for the microbial assimilation of C1 substrates. Here we provide perspective on this debate, using recent work in E. coli and the methylotrophic acetogen Eubacterium limosum as case studies.

Automated summary

Recent metabolic engineering efforts to import C1 catabolic pathways into non-methylotrophic bacteria have led to synthetic strains growing on methanol, but their growth rates and product yields are still inferior to native methylotrophs. Moreover, the development of genetic engineering tools has made native C1 utilizers more tractable, raising the question of whether it is better to use an engineered strain or a native host for the microbial assimilation of C1 substrates.