Pan-genome Analysis Reveals Comparative Genomic Features of Central Metabolic Pathways in Methylorubrum extorquens

Methylobacterium is a genus belonging to the pink-pigmented facultative methylotrophs, which can use C1 substrates as a sole carbon source. Methylorubrum extorquens (formerly Methylobacterium extorquens) is a potentially valuable bacteria in methanol-based bioindustry producing high-value-added chemicals. Thus, it is critical to understand the core metabolic pathways of M. extorquens strains for further advancement as a platform bacterium in the bioindustry. However, there are no reported systems biological approaches comparing different M. extorquens strains. This paper focuses on comparing the genomic properties of seven completely sequenced M. extorquens strains, including M. extorquens PA1, which was re-sequenced, and M. extorquens ATCC 55366, which was newly sequenced in this study. Pan-genome analysis indicated that a total of 10,431 ortholog clusters composed the pan-genome of these M. extorquens strains, including 3,507 core genome, 1,860 accessory genome, and 5,064 unique genome clusters. The functional annotation discovered that genes related to signal transduction were the most abundant in the pan-genome. Pan-genome analysis of two different habitat-specific groups revealed that the strains isolated from various soil environments had a higher percentage of genes involved in mobilome in their core genome. Subsequent exploration for secondary metabolite biosynthesis clusters denoted the unique ability of M. extorquens AM1 to produce various toblerols. M. extorquens PA1 could be a strong candidate for industrial strain development because of its minimal genome size with fully conserved central metabolism. This study provides the first inclusive insight into the differences in genomic characteristics of central metabolic networks of M. extorquens.