Sharing vitamins: Cobamides unveil microbial interactions

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Science  03 Jul 2020:
Vol. 369, Issue 6499, eaba0165
DOI: 10.1126/science.aba0165

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Nutritional interdependencies

Bacteria and archaea show a wide range of nutritional specialism. Not every organism can synthesize essential components and may need to trade for them. Taking as an example a diverse and interesting family of enzyme cofactors—the cobalt-containing cobamides, which include vitamin B12—Sokolovskaya et al. reviewed the interdependencies among microorganisms for this suite of nutrients. Cobamides are required for many processes, from catabolism of carbon sources to nucleotide biosynthesis, and are needed by a majority of microbes, from those in the gut to those in the oceans. Availability of cobamides is patchy and habitat specific, and nonspecific scavenging may not be adequate to obtain a specific cobamide structure required by an organism. Therefore, a variety of mutualisms have evolved to deliver and import specific structural variants of cobamides between organisms or among consortia of eukaryotes and prokaryotes by an equal variety of subtle and distinct mechanisms.

Science, this issue p. 48

Structured Abstract


Nearly every plant, animal, and environment on earth is host to a diverse community of microorganisms that influence each other and their environment. Microorganisms within communities interact on a molecular level by competing for resources or sharing valuable nutrients (such as cobamides, which we highlight in this Review). Such molecular interactions influence the physiology of individual microorganisms as well as the overall function of communities. Therefore, studying how microbes interact with each other is essential for understanding, and potentially interfering with, microbial processes that influence human and environmental health.

Cobamides are structurally diverse, cobalt-containing cofactors, the most familiar of which is vitamin B12 (also known as cobalamin). Since the initial discovery of vitamin B12 as the treatment for the disease pernicious anemia in 1948, microbiologists have identified more than a dozen cobamides—B12 and analogs—that are produced exclusively by bacteria and archaea. Although vitamin B12 is most widely appreciated for its role in human health, B12 and other cobamides also play important roles in the context of microbial communities. Microbes use cobamides as catalysts for chemical reactions involved in amino acid synthesis, carbon metabolism, and many other functions. Importantly, microorganisms in all domains of life need cobamides, but most depend on surrounding species to produce this nutrient, which results in a network of cobamide-dependent interactions. A nuance of these interactions, derived from the structural diversity of cobamides, is that organisms are selective toward particular cobamides, and different species have distinct cobamide preferences. As a result, cobamides mediate specific associations among microorganisms and can have substantially different effects on the growth and metabolism of different species. Therefore, cobamide sharing can serve as a model for the complexity of microbial interactions and provide a useful system to study the mechanisms that influence community composition and function.


Our current understanding of the roles of cobamides in microbial communities is the result of multilayered approaches to studying cobamide biology. Historically, the differential effects of cobamides have been investigated using laboratory cultures of single species and the biochemical characterization of cobamide-dependent enzymes. However, it is only with comparative genomic analyses of thousands of microbial species that researchers have begun to fully recognize the prevalence of cobamide sharing among microorganisms. Several newly described cocultures of two to three microbial species bridge molecular analysis and community-wide studies, and these cocultures provide experimental systems for probing the mechanisms and dynamics of cobamide sharing. Integrating discoveries across these different scales of analysis is a valuable strategy for understanding the functions of important molecules in microbial communities.


The structural diversity, functional specificity, and widespread use of cobamides by microorganisms have led researchers to speculate that cobamides could be used as tools to manipulate microbial community composition and function to improve environmental or human health. Performing cobamide-based manipulations in a controlled manner requires a greater understanding of how specific cobamides affect particular members of a community or might disrupt existing microbial interactions. Further integrating molecular approaches with community-wide studies will pave the way for understanding complex microbial communities in increasing mechanistic detail and may enable potential applications of cobamides in human health, agriculture, and industrial production.

Cobamides as models for studying microbial interactions.

Cobamides are a class of enzyme cofactors that are used for a wide variety of metabolic functions. They contain a catalytic upper ligand (R) and a structurally variable region (shown in blue, red, or green) that influences organisms’ metabolism and growth. Studies of cobamide biology on multiple scales—from enzymes to microbial communities—have revealed that cobamides constitute an effective model system for studying the complexity of microbial interactions.


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.

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