Methylotrophy in <i>Methylobacterium extorquens</i> AM1 from a Genomic Point of View

Methylotrophy is defined as the ability to “grow at the expense of reduced carbon compounds containing one or more carbon atoms but containing no carbon-carbon bonds” (3). It is an intriguing example of microbial metabolic agility, with the use of a class of chemicals disregarded by the majority of organisms. Even though the ability to grow methylotrophically was first discovered in the early 1900s (cited in reference 3), it was not until the 1960s to 1970s that an understanding of the biochemical nature of this capability started to emerge. Fascination with methylotrophy in those years was fueled by the commercial interest in single-cell protein production, and as a result, the specific details of the biochemistry of methylotrophy began to be revealed. Enzymes for the primary oxidation of C1 substrates such as methanol dehydrogenase and methylamine dehydrogenase were characterized, and distinct modes of C1 assimilation, such as the ribulose monophosphate cycle and the serine cycle were discovered. The biochemical processes involved in methylotrophy that were known by 1982 are described in detail in the now classic book Biochemistry of Methylotrophs by Christopher Anthony (3). In the 20 years following the publication of Biochemistry of Methylotrophs, a few additional methylotrophy biochemical pathways have been discovered, such as the pathway for C1 transfer linked to methanopterin and methanofuran, which solved the long-standing mystery of formaldehyde oxidation in many methylotrophs (15, 53), and novel pathways for primary C1 oxidation, such as the pathways for degradation of chlorinated methanes and methanesulfonic acid (21, 50). The knowledge concerning the biochemistry and physiology of methylotrophic organisms accumulated over the past three decades suggests a new framework for understanding methylotrophy as a novel metabolic mode. In this framework, methylotrophy is envisioned as a set of specific metabolic functional modules, with different combinations of such modules being present in different methylotrophs (Fig. ​(Fig.11 for the methylotrophic metabolic modules in Methylobacterium extorquens AM1). However, until recently, a number of important details of these modules were missing, and so the picture remained incomplete. The availability of two unfinished genome sequences for the important model organisms M. extorquens AM1 (http://www.integratedgenomics.com/genomereleases.html#list6)and Methylococcus capsulatus Bath (http://tigrblast.tigr.org/ufmg/) is transforming our understanding of methylotrophy. Annotation of these two genomes combined with functional analysis will delineate the set of genes and functions that is both sufficient and necessary to define a methylotroph. Expanding genomic analyses to include other groups of methylotrophs will in turn provide clues to the origins of methylotrophy and the evolution of various methylotrophic pathways. In this publication, we summarize the existing knowledge of the genes involved in methylotrophic pathways in M. extorquens AM1, analyze its yet unfinished genome with respect to location and clustering of methylotrophy genes, and present a comprehensive list of methylotrophy genes and enzymes known at this time in M. extorquens AM1 (Table ​(Table11). FIG. 1. Methylotrophy metabolic modules in M. extorquens AM1. Known genes are in italic. For simplicity, redox reactions in the assimilatory pathways are not indicated. For details, refer to the references given in Table ​Table11. TABLE 1. Methylotrophy genes in M. extorquens AM1