A novel biocatalytic approach for the large-scale production of S-2-ethoxy-3-(4-hydroxyphenyl)propanoic acid S-1 from its racemic ethylester rac-2 by enantioselective hydrolysis has been developed. S-1 is an important building block in the synthesis of PPARα and -γ agonists such as Ragaglitazar [NNC 61-0029 ((−)DRF2725)]. The development history comprises enzyme screening, biocatalyst and process optimization, and scale-up to pilot plant. The project was thereby highly interdisciplinary by combining biotechnology and chemistry technologies. The final process was successfully run on a 44-kg pilot scale in 43−48% yields and with high enantiomeric purities (98.4−99.6% ee).