Efficient Synthesis of a Chiral Precursor for Angiotensin-Converting Enzyme (ACE) Inhibitors in High Space-Time Yield by a New Reductase without External Cofactors

A new reductase, CgKR2, with the ability to reduce ethyl 2-oxo-4-phenylbutyrate (OPBE) to ethyl (<i>R</i>)-2-hydroxy-4-phenylbutyrate ((<i>R</i>)-HPBE), an important chiral precursor for angiotensin-converting enzyme (ACE) inhibitors, was discovered. For the first time, (<i>R</i>)-HPBE with >99% <i>ee</i> was produced via bioreduction of OPBE at 1 M without external addition of cofactors. The space-time yield (700 g·L^–1·d^–1) was 27 times higher than the highest record