Bacilli glutamate dehydrogenases diverged via coevolution of transcription and enzyme regulation

Lianet Noda-Garcia, Maria Luisa Romero Romero, Liam M. Longo, Ilana Kolodkin-Gal, Dan S. Tawfik*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


The linkage between regulatory elements of transcription, such as promoters, and their protein products is central to gene function. Promoter–protein coevolution is therefore expected, but rarely observed, and the manner by which these two regulatory levels are linked remains largely unknown. We study glutamate dehydrogenase—a hub of carbon and nitrogen metabolism. In Bacillus subtilis, two paralogues exist: GudB is constitutively transcribed whereas RocG is tightly regulated. In their active, oligomeric states, both enzymes show similar enzymatic rates. However, swaps of enzymes and promoters cause severe fitness losses, thus indicating promoter–enzyme coevolution. Characterization of the proteins shows that, compared to RocG, GudB's enzymatic activity is highly dependent on glutamate and pH. Promoter–enzyme swaps therefore result in excessive glutamate degradation when expressing a constitutive enzyme under a constitutive promoter, or insufficient activity when both the enzyme and its promoter are tightly regulated. Coevolution of transcriptional and enzymatic regulation therefore underlies paralogue-specific spatio-temporal control, especially under diverse growth conditions.

Original languageAmerican English
Pages (from-to)1139-1149
Number of pages11
JournalEMBO Reports
Issue number7
StatePublished - Jul 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 The Authors


  • Bacillus subtilis
  • enzyme evolution
  • glutamate dehydrogenases
  • paralogue specialization


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