Genome analyses predict that the cofactor cobalamin (vitamin B12, called B12 herein) is produced by only one-third of all prokaryotes but almost all encode at least one B12-dependent enzyme, in most cases methionine synthase. This implies that the majority of prokaryotes relies on exogenous B12 supply and interacts with producers. B12 consists of a corrin ring centred around a cobalt ion and the lower ligand 5’6-dimethylbenzimidazole (DMB). It has never been tested whether availability of this pivotal cofactor, DMB or its intermediate α-ribazole affect growth and composition of prokaryotic microbial communities. Here we show that in the subtropical, equatorial and polar frontal Pacific Ocean supply of B12 and α-ribazole enhances heterotrophic prokaryotic production and alters the composition of prokaryotic and heterotrophic protist communities. In the polar frontal Pacific, the SAR11 clade and Oceanospirillales increased their relative abundances upon B12 supply. In the subtropical Pacific, Oceanospirillales increased their relative abundance upon B12 supply as well but also downregulated the transcription of the btuB gene, encoding the outer membrane permease for B12. Surprisingly, Prochlorococcus, known to produce pseudo-B12 and not B12, exhibited significant upregulation of genes encoding key proteins of photosystem I + II, carbon fixation and nitrate reduction upon B12 supply in the subtropical Pacific. These findings show that availability of B12 and α-ribazole affect growth and composition of prokaryotic and protist communities in oceanic systems thus revealing far-reaching consequences of methionine biosynthesis and other B12-dependent enzymatic reactions on a community level.