The large scale synthesis of "unnatural" amino acids.
The introduction of a stereogenic centre to produce an "unnatural" amino acid can be accomplished in a variety of ways ranging from asymmetric hydrogenation to biotransformations based on transaminase enzymes. Our transaminase approach can be used to access a wide variety of L- and D-amino acids from an alpha-keto acid substrate. It is run as a whole cell biotransformation and uses coupled enzyme systems. In addition, formation of amino acids with small side chains, such as 2-aminobutyrate, can cause significant isolation problems due to the presence of small amounts of other amino acids, such as alanine. The improvements we have made to the approach are illustrated with 2-aminobutyrate as the example. Aspartic acid is used as the amino donor and gives rise to the formation of pyruvate, a substrate for the transaminase enzymes. We have now developed an alternative approach where lysine is used as the amino donor to allow formation of a cyclic by-product that is removed from the equilibrium.
Ager
D J
DJ
NSC Technologies, A Division of Great Lakes Fine Chemicals, 601 East Kensington Road, Mount Prospect, IL 60056, USA.
Fotheringham
I G
IG
Li
T
T
Pantaleone
D P
DP
Senkpeil
R F
RF
D000596:Amino Acids / Q000378:metabolism*; D000613:Aminobutyrates / Q000378:metabolism*; D001224:Aspartic Acid / Q000378:metabolism; D001483:Base Sequence; D002087:Butyrates / Q000378:metabolism; D002478:Cells, Cultured; D003001:Cloning, Molecular; D020650:Combinatorial Chemistry Techniques; D017931:DNA Primers; D005798:Genes, Bacterial; D013912:Threonine / Q000378:metabolism; D013913:Threonine Dehydratase / Q000235:genetics; D000637:Transaminases / Q000378:metabolism
D000596:Amino Acids; D000613:Aminobutyrates; D002087:Butyrates; D017931:DNA Primers; D013912:Threonine; D001224:Aspartic Acid; C005087:alpha-ketobutyric acid; C012223:alpha-aminobutyric acid; D000637:Transaminases; D013913:Threonine Dehydratase