A counter-enzyme complex regulates glutamate metabolism in Bacillus subtilis

Nat Chem Biol. 2022 Feb;18(2):161-170. doi: 10.1038/s41589-021-00919-y. Epub 2021 Dec 20.


Multi-enzyme assemblies composed of metabolic enzymes catalyzing sequential reactions are being increasingly studied. Here, we report the discovery of a 1.6 megadalton multi-enzyme complex from Bacillus subtilis composed of two enzymes catalyzing opposite ('counter-enzymes') rather than sequential reactions: glutamate synthase (GltAB) and glutamate dehydrogenase (GudB), which make and break glutamate, respectively. In vivo and in vitro studies show that the primary role of complex formation is to inhibit the activity of GudB. Using cryo-electron microscopy, we elucidated the structure of the complex and the molecular basis of inhibition of GudB by GltAB. The complex exhibits unusual oscillatory progress curves and is necessary for both planktonic growth, in glutamate-limiting conditions, and for biofilm growth, in glutamate-rich media. The regulation of a key metabolic enzyme by complexing with its counter enzyme may thus enable cell growth under fluctuating glutamate concentrations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacillus subtilis / genetics
  • Bacillus subtilis / metabolism*
  • Bacterial Proteins
  • Gene Expression Regulation, Bacterial / physiology*
  • Gene Expression Regulation, Enzymologic / physiology*
  • Glutamate Dehydrogenase / genetics
  • Glutamate Dehydrogenase / metabolism*
  • Glutamate Synthase / genetics
  • Glutamate Synthase / metabolism*
  • Glutamic Acid / biosynthesis*


  • Bacterial Proteins
  • Glutamic Acid
  • Glutamate Synthase
  • Glutamate Dehydrogenase