Frank Ferrer-González, Katherine R. Heal, Joshua S. Sacks, Yarinet Romero-Maysonet, Anna Finch, Laura T. Carlson, Lisa S. Y. Coe, Zinka Bartolek, Claudia B. Luthy, Moira Gaffney, Sabine Angier, Samantha E. Flynn, Chiara I. Bachmann Gómez, Jensen M. L. Dunn, Kenzie Bay, Lia A. Yamamoto, Matthew Tien, E. Virginia Armbrust, Bryndan P. Durham, Oscar A. Sosa, Anitra E. Ingalls
Homarine (N-methylpicolinic acid) is a ubiquitous marine metabolite produced by phytoplankton and noted for its infochemical properties among marine animals, yet its microbial degradation pathways are uncharacterized. Here we identify a conserved operon (homABCDER) that mediates homarine catabolism in bacteria using comparative transcriptomics, mutagenesis and targeted knockouts. Phylogenetic and genomic analyses show that this operon is distributed across abundant bacterial clades, including coastal copiotrophs (for example, Rhodobacterales) and open-ocean oligotrophs (for example, SAR11, SAR116), and in genomes from non-marine environments. High-resolution mass spectrometry revealed N-methylglutamic acid and glutamic acid as key metabolic products of homarine in both model and natural systems, with N-methyl-glutamate dehydrogenase catalysing their conversion. Metatranscriptomics showed responsive and in situ expression of hom genes aligned with homarine availability. These findings uncover the genetic and metabolic basis of homarine degradation, establish its ecological relevance and highlight homarine as a versatile growth substrate that feeds into central metabolism via glutamic acid in diverse marine bacteria.