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Summary: NATURE BIOTECHNOLOGY VOL 18 MARCH 2000 http://biotech.nature.com 317
The fine chemicals industry is turning increasingly to biological syn-
thesis routes to fulfill the rapidly growing demand for enantiomeri-
cally pure pharmaceuticals1. The rapidly changing product demands
that are typical for chiral intermediates, however, can limit the abili-
ty of biocatalysis to compete with other technologies. One reason is
that enantioselectivity is often substrate-dependent, with the conse-
quence that available enzymes are only useful for a limited spectrum
of products. Even slight modifications in the chiral product can
necessitate a new search for a suitable biocatalyst.
The hydantoinase process is well established for the industrial pro-
duction of various D- and L-amino acids2,3, which are valuable pre-
cursors of antibiotics and other drugs4. Arthrobacter sp. DSM9771, for
example, is used as a whole-cell catalyst for the commercial produc-
tion of natural and nonnatural L-amino acids from D,L-5-monosub-
stituted hydantoins5. However, this process cannot be used to produce
certain L-amino acids such as L-methionine (L-Met), because the
hydantoinase exhibits inverted enantioselectivity on the (racemic)
hydantoin substrate6. The preference of the enzyme for D-5-(2-
methylthioethyl)hydantoin (D-MTEH) leads to accumulation of D-
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