An active enzyme constructed from a 9-amino acid alphabet.
Nature employs a set of 20 amino acids to produce a repertoire of protein structures endowed with sophisticated functions. Here, we combined design and selection to create an enzyme composed entirely from a set of only 9 amino acids that can rescue auxotrophic cells lacking chorismate mutase. The simplified protein captures key structural features of its natural counterpart but appears to be somewhat less stable and more flexible. The potential of a dramatically reduced amino acid alphabet to produce an active catalyst supports the notion that primordial enzymes may have possessed low amino acid diversity and suggests that combinatorial engineering strategies, such as the one used here, may be generally applied to create enzymes with novel structures and functions.
Walter
Kai U
KU
Laboratory of Organic Chemistry, Swiss Federal Institute of Technology, ETH Hönggerberg, Zürich.
Vamvaca
Katherina
K
Hilvert
Donald
D
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis* / Q000737:chemistry; D002826:Chorismate Mutase / Q000737:chemistry* / Q000378:metabolism*; D004795:Enzyme Stability; D019143:Evolution, Molecular; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018583:Pliability; D011487:Protein Conformation; D015202:Protein Engineering / Q000379:methods*; D017386:Sequence Homology, Amino Acid; D013696:Temperature
D000596:Amino Acids; D002826:Chorismate Mutase