Decreasing peptide deformylase activity is a beneficial strategy for increasing formaldehyde resistance in Methylobacterium extorquens.

A single missense mutation in the evolved def allele (def evo ) of Methylobacterium extorquens lowers peptide deformylase activity and increases formaldehyde resistance.

• Why it matters: Cells face unavoidable formaldehyde toxicity, but the protective strategies—especially in methylotrophs where formaldehyde is a central intermediate—remain poorly defined.
• What they did: The authors characterized def evo and measured reduced PDF activity both in vitro and in vivo, then used transcriptomics to assess pleiotropic and stress-specific responses.
• The result: The def evo allele selectively alleviates exogenous formaldehyde stress, while revealing a trade-off in heat shock resistance and suggesting altered protein metabolism can mitigate formaldehyde damage.

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