The formaldehyde stress response systems
As a methylotroph, Methylobacterium can grow on reduced one-carbon compounds and benefit from their association with plants by utilizing methanol emitted from plant tissues. Methanol growth uses high-flux oxidative pathways that generate formaldehyde as an obligate intermediate; formaldehyde is, therefore, a central metabolite and a potential stressor. While subsequent formaldehyde utilization is well-characterized, little is known about the cellular consequences of formaldehyde imbalance in Methylobacterium or the mechanisms used to maintain intracellular homeostasis and avert/repair cellular damage. By studying formaldehyde stress in a methylotroph we focus an organism primed to encounter formaldehyde at higher concentrations than most. We aim to characterize formaldehyde specific stress response systems and understand how the cell coordinates them with general stress response systems to protect itself from this potent endogenous toxin.
Transition to methylotrophy
The metabolic flexibility of Methylobacterium enables them to independently use or co-consume single- and multi-carbon substrates. In the nutrient poor phyllosphere (aerial parts of plants) temporal fluctuations in methanol availability may require Methylobacterium to frequently adapt to and from methylotrophic metabolism. The switch to methylotrophic growth leads to metabolic imbalance as cells redistribute metabolic flux and formaldehyde bursts are known to occur. Formaldehyde stress response systems that regulate cellular processes at the transcriptional and translational levels optimize the transition to methylotrophic metabolism. We are using a number of approaches, including experimental evolution, to investigate the formaldehyde-centric cellular strategies involved in the transitions between the different modes of growth.
Effect of metabolic stress in the phyllosphere
Methylobacterium species are ubiquitous plant colonizers that promote seed germination as well as plant growth and development. Methylobacterium is best-known for occupying a particular nutrient niche on plants by using plant-generated methanol, which gives them a competitive advantage during colonization. The central role of toxic formaldehyde in methanol-based growth creates a scenario where cellular coordination and response to metabolic imbalance is critical. We are probing the advantage of formaldehyde-specific stress response systems in natural habitats via mutant analysis in planta and assessing how altering metabolic control points changes the dynamics between M. extorquens and its plant hosts.