Bioprocess design guided by in situ substrate supply and product removal: Process intensification for synthesis of (S)-1-(2-chlorophenyl)ethanol

► o-Chloroacetophenone and its reduction product are highly toxic to enzymes and cells. ► Properties of substrate and product guided comprehensive bioprocess engineering. ► Substrate supply and product removal were optimized. ► Mass transfer limitations were overcome by cell permeabilization. ► (S)-1-(2-chlorophenyl)ethanol was obtained in high optical purity and yield.