Lanthanide-Dependent Methanol Dehydrogenase XoxF Confers a Competitive Advantage to Sinorhizobium meliloti During Symbiosis with Medicago sativa

The recent discovery of the lanthanide (Ln)-dependent methanol dehydrogenase (Ln-MDH) XoxF has expanded the spectrum of bacteria recognized for methylotrophic metabolism. Many bacteria, including rhizobia, have historically escaped being categorized as methylotrophs because they exclusively produce XoxF-type Ln-MDHs and entirely lack the long-studied calcium-dependent MDH MxaFI. We report that the XoxF-type Ln-MDH encoded by the smb20173 gene is the sole MDH that supports methylotrophic growth of Sinorhizobium meliloti. The lanthanides that consistently supported growth of S. meliloti in minimal media with methanol included lanthanum, cerium, praseodymium, and neodymium. Based on genome, whole-transcriptome, and mutant phenotype analyses, we propose a metabolic model for Ln-dependent methylotrophy in S. meliloti wherein oxidation of one-carbon compounds, such as methanol, generate the reducing power needed to assimilate carbon via the Calvin–Benson–Bassham cycle. By investigating how these newfound insights into lanthanides reshape our understanding of the methylotrophic capabilities of rhizobia, we explored how methanol produced by plants has the potential to create a nutritional niche in the rhizosphere. Using a Medicago sativa (alfalfa) nodule occupancy assay, we found that a xoxF mutant strain was outcompeted by the wild-type strain only when lanthanides were available, suggesting that Ln-dependent methylotrophy promotes an efficient rhizobia–legume symbiosis. [Formula: see text] Copyright © 2026 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .