Prediction and biochemical demonstration of a catabolic pathway for the osmoprotectant proline betaine

Ritesh Kumar, Suwen Zhao, Matthew W. Vetting, B. Mc Kay Wood, Ayano Sakai, Kyuil Cho, José Solbiati, Steven C. Almo, Jonathan V. Sweedler, Matthew P. Jacobson, John A. Gerlt, John E. Cronan

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Abstract

Through the use of genetic, enzymatic, metabolomic, and structural analyses, we have discovered the catabolic pathway for proline betaine, an osmoprotectant, in Paracoccus denitrificans and Rhodobacter sphaeroides. Genetic and enzymatic analyses showed that several of the key enzymes of the hydroxyproline betaine degradation pathway also function in proline betaine degradation. Metabolomic analyses detected each of the metabolic intermediates of the pathway. The proline betaine catabolic pathway was repressed by osmotic stress and cold stress, and a regulatory transcription factor was identified. We also report crystal structure complexes of the P. denitrificans HpbD hydroxyproline betaine epimerase/proline betaine racemase with L-proline betaine and cis-hydroxyproline betaine.

Original languageEnglish (US)
Article numbere00933-13
JournalmBio
Volume5
Issue number1
DOIs
StatePublished - Feb 11 2014

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ASJC Scopus subject areas

  • Microbiology
  • Virology

Cite this

Kumar, R., Zhao, S., Vetting, M. W., Wood, B. M. K., Sakai, A., Cho, K., Solbiati, J., Almo, S. C., Sweedler, J. V., Jacobson, M. P., Gerlt, J. A., & Cronan, J. E. (2014). Prediction and biochemical demonstration of a catabolic pathway for the osmoprotectant proline betaine. mBio, 5(1), [e00933-13]. https://doi.org/10.1128/mBio.00933-13