Abstract
The kingdoms of life share many small molecule cofactors and coenzymes. Molybdenum cofactor (Moco) is synthesized by many archaea, bacteria, and eukaryotes, and is essential for human development. The genome of Caenorhabditis elegans contains all of the Moco biosynthesis genes, and surprisingly these genes are not essential if the animals are fed a bacterial diet that synthesizes Moco. C. elegans lacking both endogenous Moco synthesis and dietary Moco from bacteria arrest development, demonstrating interkingdom Moco transfer. Our screen of Escherichia coli mutants identifies genes necessary for synthesis of bacterial Moco or transfer to C. elegans. Developmental arrest of Moco-deficient C. elegans is caused by loss of sulfite oxidase, a Moco-requiring enzyme, and is suppressed by mutations in either C. elegans cystathionine gamma-lyase or cysteine dioxygenase, blocking toxic sulfite production from cystathionine. Thus, we define the genetic pathways for an interkingdom dialogue focused on sulfur homeostasis.
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Acknowledgements
We thank the Caenorhabditis Genetics Center, M. Han, V. Ambros, and S. Mitani for providing C. elegans strains. We thank M.-A. Félix for providing wild bacterial isolates and the National BioResource Project (NIG, Japan) for providing the Keio E. coli knockout collection. This work was funded by an NIH Grant (5R01GM044619-26) to G.R. and a Damon Runyon Fellowship (DRG-2293-16) to K.W.
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K.W. and G.R. designed experiments, and K.W. performed experiments. K.W. and G.R. wrote the manuscript.
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Warnhoff, K., Ruvkun, G. Molybdenum cofactor transfer from bacteria to nematode mediates sulfite detoxification. Nat Chem Biol 15, 480–488 (2019). https://doi.org/10.1038/s41589-019-0249-y
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DOI: https://doi.org/10.1038/s41589-019-0249-y
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