Sharing vitamins: Cobamides unveil microbial interactions

Abstract

Microbial communities are essential to fundamental processes on Earth. Underlying the compositions and functions of these communities are nutritional interdependencies among individual species. One class of nutrients, cobamides (the family of enzyme cofactors that includes vitamin B₁₂), is widely used for a variety of microbial metabolic functions, but these structurally diverse cofactors are synthesized by only a subset of bacteria and archaea. Advances at different scales of study-from individual isolates, to synthetic consortia, to complex communities-have led to an improved understanding of cobamide sharing. Here, we discuss how cobamides affect microbes at each of these three scales and how integrating different approaches leads to a more complete understanding of microbial interactions.

Fig. 1.. Structural diversity of cobamides.

(A) The chemical structure of cobalamin (B₁₂), the most well-known cobamide. Cobamides are characterized by a corrin ring (a contracted porphyrin, similar to the macrocycles of heme and chlorophyll) which houses a cobalt ion. Exchangeable upper ligands (R₁) give cobamides versatile chemical reactivity (6). Lower ligands differ between cobalamin and other cobamides. The red asterisk indicates a methyl group that is absent in norcobamides (35, 36). (B) Three lower ligand structural classes are shown, which have multiple variable regions (R₂ to R₆).

Fig. 2.. Cobamide sharing in model microbial consortia.

(A) Algae-bacteria mutualism. L. rostrata requires cobalamin produced by M. loti as a cofactor for its methionine synthase (MetH), and M. loti uses fixed carbon produced by L. rostrata (40, 56, 57). (B) Amoeba-prey consortium. V. cholerae remodels pseudocobalamin produced by Synechococcus elongatus to produce cobalamin, which can be used by the amoeba LPG3 for MetH activity (25, 29). (C) Cocultures of A. muciniphila with other human gut bacteria. Cobamide production by E. hallii causes a switch in the mucin degradation product generated by A. muciniphila, from succinate to propionate (62). Cobamide (Co-containing cartoon) with blue indicates cobalamin, and that with red indicates pseudocobalamin.

Fig. 3.. Distribution of cobamide production and use among bacteria.

The percentages of species that use and produce cobamides are derived from published bioinformatic analyses of 540 bacterial genomes from diverse environments (column a) (13), 311 human gut bacterial genomes (column b) (18), and 11,463 bacterial genomes from diverse environments (column c) (5).

Fig. 4.. Factors in complex chemical environments that can modulate cobamide physiology.

RS, riboswitch.