A Eukaryote-Featured\nMembrane Phospholipid Enhances\nBacterial Formaldehyde Tolerance and Assimilation of One-Carbon Feedstocks

Efficient bioassimilation of one-carbon (C1) feedstocks\nis often\nhindered by the toxicity of C1 substrates and/or intermediates. We\ncompared the toxicity of several common C1 substrates/intermediates\nand found that formaldehyde imposes the highest toxicity on the representative\nbacterium Escherichia coli. Besides\ncausing chromosomal DNA and protein damage effects, here, we revealed\nthat formaldehyde greatly impairs cell membranes. To this end, here,\nwe sought to remodel the cell membrane of E. coli by introducing a non-native, eukaryote-featured membrane phospholipid\ncomposition, phosphatidylcholine (PC). This engineered E. coli strain exhibited significantly increased\nmembrane integrity, resulting in enhanced formaldehyde tolerance.\nWhen applied to C1 assimilation, the PC-harboring E.\ncoli consumed up to 4.7 g/L methanol, which is 23-fold\nhigher than that of the control strain (0.2 g/L). In summary, the\npresent study highlights the detrimental impact of formaldehyde-induced\nmembrane damage and thus underscores the significance of membrane\nremodeling in enhancing formaldehyde tolerance and facilitating the\nassimilation of C1 substrates.