Bacilli glutamate dehydrogenases diverged via coevolution of transcription and enzyme regulation

• Published in: EMBO reports Vol. 18; no. 7; pp. 1139 - 1149
• Main Authors: Noda‐Garcia, Lianet, Romero Romero, Maria Luisa, Longo, Liam M, Kolodkin‐Gal, Ilana, Tawfik, Dan S
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.07.2017; Blackwell Publishing Ltd; John Wiley and Sons Inc
• Subjects: Bacilli; Bacillus subtilis; Bacillus subtilis - enzymology; Bacillus subtilis - genetics; Bacillus subtilis - growth & development; Bacterial Proteins - genetics; Biological Coevolution; Coevolution; Control; Dehydrogenase; Dehydrogenases; EMBO15; EMBO21; EMBO23; Enzymatic activity; enzyme evolution; Enzymes; Fitness; Gene Expression Regulation, Bacterial; Gene regulation; Genetic Fitness; Glutamate dehydrogenase; Glutamate Dehydrogenase - genetics; glutamate dehydrogenases; Glutamic Acid - metabolism; Growth conditions; Incompatibility; Metabolism; Mutation; Nitrogen metabolism; paralogue specialization; pH effects; Promoter Regions, Genetic; Promoters; Proteins; Regulation; Regulatory sequences; Transcription; paralogue specialization; enzyme evolution; glutamate dehydrogenases; Bacillus subtilis
• ISSN: 1469-221X; 1469-3178
• DOI: 10.15252/embr.201743990

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. Synopsis Bacilli have two glutamate dehydrogenase paralogues. Regulation has diverged from transcriptional control in one paralogue (RocG) to enzyme control in the other (GudB), thus creating incompatibility upon swaps of enzymes and regulatory regions (promoter/terminator). Swapping enzymes and regulatory regions of the Bacilli glutamate dehydrogenase paralogues reveals coevolution of transcription and enzyme regulation. Coevolution of transcriptional and enzymatic regulation underlies paralogue‐specific spatio‐temporal control. The Bacilli glutamate dehydrogenases are regulated via oligomer assembly. Graphical Abstract Bacilli have two glutamate dehydrogenase paralogues. Regulation has diverged from transcriptional control in one paralogue (RocG) to enzyme control in the other (GudB), thus creating incompatibility upon swaps of enzymes and regulatory regions.