The glycine betaine-cobalamin feedback loop drives cross-feeding between marine bacteria and algae

Hammer, J.; Staack, M.; Sperfeld, M.; Haufschild, T.; Kallscheuer, N.; Narvaez-Barragan, D. A.; Wegner, C.-E.; Kuesel, K.; Sunagawa, S.; Pohnert, G.; Schubert, T.; Segev, E.; Jogler, C.

doi:10.64898/2025.12.19.695462

bioRxiv · 10.64898/2025.12.19.695462

The glycine betaine-cobalamin feedback loop drives cross-feeding between marine bacteria and algae

Hammer, J.·Staack, M.·Sperfeld, M.·Haufschild, T.·Kallscheuer, N.·Narvaez-Barragan, D. A.·Wegner, C.-E.·Kuesel, K.·Sunagawa, S.·Pohnert, G.·Schubert, T.·Segev, E.·Jogler, C.

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Abstract

Heterotrophic bacteria supply cobalt-containing cobalamin (Cbl) to marine microalgae, which in return provide organic substrates. Such metabolic cross-feeding can regulate the species composition of prolific marine plankton and biofilms. Algal-produced glycine betaine (GB) can be catabolized by bacteria using a Cbl-dependent demethylase (MtgBCD). Yet, GBs impact on bacterial Cbl production during cross-feeding, and its control by cobalt scarcity remains elusive. Here, we demonstrate that Phaeobacter inhibens bacteria boost their Cbl production 25-fold when grown in monocultures with GB compared to glucose. During co-cultivation, P. inhibens satisfied the Cbl requirements of Gephyrocapsa huxleyi algae. Transcriptomic analysis of mono- and co-cultures revealed co-expression of mtgBCD and gbcAB genes encoding Cbl-dependent and -independent GB demethylases, respectively. Distinct growth defects of deletion mutants indicate that P. inhibens switches from Cbl-dependent to -independent GB demethylation under cobalt limitation, involving a Cbl riboswitch. Our findings suggest a positive feedback loop in which algal GB release stimulates the bacterial supply of Cbl. We predict the breakdown of this interaction under naturally occurring cobalt limitation which potentially contributes to the transient nature of algal blooms. Comparative genomics indicate that this mechanism is widespread in Rhodobacterales and other abundant marine Alphaproteobacteria, underscoring its pivotal role in global ocean productivity.

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Hammer, J., Staack, M., Sperfeld, M., Haufschild, T., Kallscheuer, N., Narvaez-Barragan, D. A., Wegner, C.-E., Kuesel, K., Sunagawa, S., Pohnert, G., Schubert, T., Segev, E., Jogler, C.. 2025-12-21. The glycine betaine-cobalamin feedback loop drives cross-feeding between marine bacteria and algae. https://doi.org/10.64898/2025.12.19.695462

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