Fig. 1

Amino acid productions and codon usage. a Global productions of amino acids (left), the annual productions (right, represented by color intensity), and the fermentation titer (right, represented by bar height) for nine selected amino acids. b After taken up by the cells (i), the amino acid analogues (orange square) compete with the corresponding natural amino acids (blue hexagon) for the finite tRNAs, a step catalyzed by the aminoacyl-tRNA synthetase (aaRS). The analogues could be blocked (ii) or pumped outside of the cells (iii). c Codon usage and the fraction of tRNAs (bubble diameter) in E. coli²². The fraction of individual tRNA out of the total tRNA was derived from E. coli W1485, a K strain derivative at a growth rate of 0.4 doublings h^–1. d For an exogenous gene, replacing its codons (e.g. leucine codon) with synonymous ones that are recognized by the most abundant tRNAs for a specific host would typically improve the expression of the desired protein (upper box). On the contrary, the rare tRNAs have lower chances to be charged with the corresponding amino acids, switching to the rare alternatives (e.g. leucine codon CTA for E. coli) that pair with the low-abundance tRNAs would dramatically slow down protein expression (lower box). Theoretically, the retarded protein expression should be restored by increased intracellular concentrations of the corresponding amino acids