Efficient Synthesis of Chiral Aryl Alcohol with a Novel Kosakonia radicincitans Isolate in Tween 20/L-carnitine: Lysine-Containing Synergistic Reaction System.

Abstract

Chiral trifluoromethyl alcohols as vital intermediates are of great interest in fine chemicals and especially in pharmaceutical synthesis. In this work, a novel isolate Kosakonia radicincitans ZJPH202011 was firstly employed as biocatalyst for the synthesis of (R)-1-(4-bromophenyl)-2,2,2-trifluoroethanol ((R)-BPFL) with good enantioselectivity. By optimizing fermentation conditions and bioreduction parameters in aqueous buffer system, the substrate concentration of 1-(4-bromophenyl)-2,2,2-trifluoroethanone (BPFO) was doubled from 10 to 20mM, and the enantiomeric excess (ee) value for (R)-BPFL increased from 88.8 to 96.4%. To improve biocatalytic efficiency by strengthening the mass-transfer rate, natural deep-eutectic solvents, surfactants and cyclodextrins (CDs) were introduced separately in the reaction system as cosolvent. Among them, L-carnitine: lysine (C: Lys, molar ratio 1:2), Tween 20 and γ-CD manifested higher (R)-BPFL yield compared with other same kind of cosolvents. Furthermore, based on the excellent performance of both Tween 20 and C: Lys (1:2) in enhancing BPFO solubility and ameliorating cell permeability, a Tween 20/C: Lys (1:2)-containing integrated reaction system was then established for efficient bioproduction of (R)-BPFL. After optimizing the critical factors involved in BPFO bioreduction in this synergistic reaction system, BPFO loading increased up to 45mM and the yield reached 90.0% within 9h, comparatively only 37.6% yield was acquired in neat aqueous buffer. This is the first report on K. radicincitans cells as new biocatalyst applied in (R)-BPFL preparation, and the developed Tween 20/C: Lys-containing synergistic reaction system has great potential for the synthesis of various chiral alcohols.