Complex regulation in a Comamonas platform for diverse aromatic carbon metabolism

Rebecca A. Wilkes, Jacob Waldbauer, Austin Caroll, Manuel Nieto-Domínguez, Darren J. Parker, Lichun Zhang, Adam M. Guss, Ludmilla Aristilde*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Critical to a sustainable energy future are microbial platforms that can process aromatic carbons from the largely untapped reservoir of lignin and plastic feedstocks. Comamonas species present promising bacterial candidates for such platforms because they can use a range of natural and xenobiotic aromatic compounds and often possess innate genetic constraints that avoid competition with sugars. However, the metabolic reactions of these species are underexplored, and the regulatory mechanisms are unknown. Here we identify multilevel regulation in the conversion of lignin-related natural aromatic compounds, 4-hydroxybenzoate and vanillate, and the plastics-related xenobiotic aromatic compound, terephthalate, in Comamonas testosteroni KF-1. Transcription-level regulation controls initial catabolism and cleavage, but metabolite-level thermodynamic regulation governs fluxes in central carbon metabolism. Quantitative 13C mapping of tricarboxylic acid cycle and cataplerotic reactions elucidates key carbon routing not evident from enzyme abundance changes. This scheme of transcriptional activation coupled with metabolic fine-tuning challenges outcome predictions during metabolic manipulations. [Figure not available: see fulltext.]

Original languageEnglish (US)
Pages (from-to)651-662
Number of pages12
JournalNature Chemical Biology
Issue number5
StatePublished - May 2023

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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