Cyanobacteria and Eukaryotic Algae Use Different Chemical Variants of Vitamin B12

Eukaryotic microalgae and prokaryotic cyanobacteria are the major components of the phytoplankton. Determining factors that govern growth of these primary producers, and how they interact, is therefore essential to understanding aquatic ecosystem productivity. Over half of microalgal species representing marine and freshwater habitats require for growth the corrinoid cofactor B-12, which is synthesized de novo only by certain prokaryotes, including the majority of cyanobacteria. There are several chemical variants of B-12, which are not necessarily functionally interchangeable. Cobalamin, the form bioavailable to humans, has as its lower axial ligand 5,6-dimethyl-benzimidazole (DMB). Here, we show that the abundant marine cyanobacterium Synechococcus synthesizes only pseudocobalamin, in which the lower axial ligand is adenine. Moreover, bioinformatic searches of over 100 sequenced cyanobacterial genomes for B-12 biosynthesis genes, including those involved in nucleotide loop assembly, suggest this is the form synthesized by cyanobacteria more broadly. We further demonstrate that pseudocobalamin is several orders of magnitude less bioavailable than cobalamin to several B-12-dependent microalgae representing diverse lineages. This indicates that the two major phytoplankton groups use a different B-12 currency. However, in an intriguing twist, some microalgal species can use pseudocobalamin if DMB is provided, suggesting that they are able to remodel the cofactor, whereas Synechococcus cannot. This species-specific attribute implicates algal remodelers as novel and keystone players of the B-12 cycle, transforming our perception of the dynamics and complexity of the flux of this nutrient in aquatic ecosystems.