Metabolic efficiency and amino acid composition in the proteomes of Escherichia coli and Bacillus subtilis

Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3695-700. doi: 10.1073/pnas.062526999.


Biosynthesis of an Escherichia coli cell, with organic compounds as sources of energy and carbon, requires approximately 20 to 60 billion high-energy phosphate bonds [Stouthamer, A. H. (1973) Antonie van Leeuwenhoek 39, 545-565]. A substantial fraction of this energy budget is devoted to biosynthesis of amino acids, the building blocks of proteins. The fueling reactions of central metabolism provide precursor metabolites for synthesis of the 20 amino acids incorporated into proteins. Thus, synthesis of an amino acid entails a dual cost: energy is lost by diverting chemical intermediates from fueling reactions and additional energy is required to convert precursor metabolites to amino acids. Among amino acids, costs of synthesis vary from 12 to 74 high-energy phosphate bonds per molecule. The energetic advantage to encoding a less costly amino acid in a highly expressed gene can be greater than 0.025% of the total energy budget. Here, we provide evidence that amino acid composition in the proteomes of E. coli and Bacillus subtilis reflects the action of natural selection to enhance metabolic efficiency. We employ synonymous codon usage bias as a measure of translation rates and show increases in the abundance of less energetically costly amino acids in highly expressed proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / analysis*
  • Amino Acids / biosynthesis
  • Amino Acids / metabolism
  • Bacillus subtilis / chemistry*
  • Bacillus subtilis / metabolism*
  • Bacterial Proteins / biosynthesis
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Bias
  • Codon / genetics
  • Energy Metabolism*
  • Escherichia coli / chemistry*
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins / biosynthesis
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Gene Expression Regulation, Bacterial
  • Genetic Code / genetics
  • Proteome / biosynthesis
  • Proteome / chemistry*
  • Selection, Genetic


  • Amino Acids
  • Bacterial Proteins
  • Codon
  • Escherichia coli Proteins
  • Proteome