Mitigating toxic formaldehyde to promote efficient utilization of C1 resources

The C1 resource is widely considered because of its abundance and affordability. In the context of extensive utilization of C1 resources by methylotrophic microorganisms, especially for methanol, formaldehyde is an important intermediate metabolite that is at the crossroads of assimilation and dissimilation pathways. However, formaldehyde is an exceedingly reactive compound that can form covalent cross-linked complexes with amine and thiol groups in cells, which causes irreversible damage to the organism. Thus, it is important to balance the intensity of the assimilation and dissimilation pathways of formaldehyde, which can avoid formaldehyde toxicity and improve the full utilization of C1 resources. This review details the source of endogenous formaldehyde and its toxicity mechanism, explaining the harm of excessive accumulation of formaldehyde to metabolism. Importantly, the self-detoxification and various feasible strategies to mitigate formaldehyde toxicity are discussed and proposed. These strategies are meant to help appropriately handle formaldehyde toxicity and accelerate the effective use of C1 resources.