New pieces to the lanthanide puzzle.

Recently, rare-earth elements lanthanides (Ln ) have emerged as enzyme cofactors of methanol dehydrogenases of the XoxF type. It is now understood that XoxF enzymes can functionally replace the alternative, calcium-dependent, MxaFI-type methanol dehydrogenases, when Ln are available. These rare-earth metals are not only essential for XoxF activity, but they also regulate gene expression, in a reverse fashion, activating the expression of XoxF and repressing the expression of MxaFI. This type of regulation has created multiple conundrums, including the details of the solubility, transport, sensing and selection mechanisms for Ln by the bacterial cells, as well as the questions relevant to the evolution of the alternative enzymes and their potentially different redox properties. Overall, the newly discovered biological activity of Ln presents a big puzzle. Ochsner et al. add several pieces to this puzzle, utilizing a model phyllosphere colonizer Methylobacterium extorquens PA1. They determine that Ln sensing by this organism can take place via both XoxF-dependent and XoxF-independent mechanisms. They also identify genes for a TonB-dependent transporter and an ABC-type transporter and demonstrate that both are essential for Ln -dependent methanol metabolism. The puzzle still requires multiple additional pieces for completion, but great strides have been made toward the goal of solving it.