Abstract
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 language | English (US) |
|---|---|
| Pages (from-to) | 651-662 |
| Number of pages | 12 |
| Journal | Nature Chemical Biology |
| Volume | 19 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 2023 |
Funding
The US National Science Foundation (NSF) Graduate Research Fellowship Program (DGE-1650441) provided support for R.A.W. Metabolomics studies were funded by a grant awarded to L.A. from the US NSF (CBET-2022854). This work was authored, in part, by Oak Ridge National Laboratory, which is managed by UT-Battelle, LLC, for the US Department of Energy (DOE) under contract DE-AC05-00OR22725. Funding was provided, in part, by the US DOE, Office of Energy Efficiency and Renewable Energy, Advanced Manufacturing Office and Bioenergy Technologies Office as part of the BOTTLE Consortium. We thank D. Salvachúa and C. Hoyt of the National Renewable Energy Laboratory (NREL) for synthesizing and supplying the 2-pyrone-4,6-dicarboxylic acid standard for quantification by HPLC. We thank G. Beckham of NREL for his feedback to early drafts of this manuscript. We acknowledge E. Hartmann of Northwestern University for granting access to their laboratory for RNA extractions. The US National Science Foundation (NSF) Graduate Research Fellowship Program (DGE-1650441) provided support for R.A.W. Metabolomics studies were funded by a grant awarded to L.A. from the US NSF (CBET-2022854). This work was authored, in part, by Oak Ridge National Laboratory, which is managed by UT-Battelle, LLC, for the US Department of Energy (DOE) under contract DE-AC05-00OR22725. Funding was provided, in part, by the US DOE, Office of Energy Efficiency and Renewable Energy, Advanced Manufacturing Office and Bioenergy Technologies Office as part of the BOTTLE Consortium. We thank D. Salvachúa and C. Hoyt of the National Renewable Energy Laboratory (NREL) for synthesizing and supplying the 2-pyrone-4,6-dicarboxylic acid standard for quantification by HPLC. We thank G. Beckham of NREL for his feedback to early drafts of this manuscript. We acknowledge E. Hartmann of Northwestern University for granting access to their laboratory for RNA extractions.
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology