Minimal Genome that Encodes Proteins with Constrained Amino Acid Repertoire

Minimal bacterial gene set comprises the genetic elements needed for survival of engineered bacterium on a rich medium. This set is estimated to include 300-350 protein-coding genes. One way of simplifying an organism with such a minimal genome even further is to constrain the amino acid content of its proteins. We used comparative genomics to examine the challenges of completely replacing the two rarest residues, cysteine and tryptophan. Drastic reduction of the content of these amino acids appears to be possible, but their complete elimination is challenging. In particular, cysteine residues in four proteins involved in ribonucleoside modifications appear to be essential, as no alternative chemistry is known for these functions