Efficient bioassimilation of one-carbon (C1) feedstocks is often hindered by the toxicity of C1 substrates and/or intermediates. We compared the toxicity of several common C1 substrates/intermediates and found that formaldehyde imposes the highest toxicity on the representative bacterium Escherichia coli. Besides causing chromosomal DNA and protein damage effects, here, we revealed that formaldehyde greatly impairs cell membranes. To this end, here, we sought to remodel the cell membrane of E. coli by introducing a non-native, eukaryote-featured membrane phospholipid composition, phosphatidylcholine (PC). This engineered E. coli strain exhibited significantly increased membrane integrity, resulting in enhanced formaldehyde tolerance. When applied to C1 assimilation, the PC-harboring E. coli consumed up to 4.7 g/L methanol, which is 23-fold higher than that of the control strain (0.2 g/L). In summary, the present study highlights the detrimental impact of formaldehyde-induced membrane damage and thus underscores the significance of membrane remodeling in enhancing formaldehyde tolerance and facilitating the assimilation of C1 substrates.
Keywords: E. coli; Formaldehyde toxicity; membrane damage; membrane remodeling; methanol assimilation; phosphatidylcholine.