Effect of additives on the asymmetric reduction of fluorinated ketones using cyanobacterium Synechocystis sp. PCC 6803

The asymmetric reduction of fluorinated ketones (1a–c) was investigated using the wild-type cyanobacterium Synechocystis sp. PCC 6803 at 25 °C for 24 h. Under red LED illumination (660 nm, 10 μmol m⁻² s⁻¹), the photosynthetic system promoted cofactor regeneration, enhancing the formation of optically active alcohols (2a–c). The effect of substrate concentration was found to significantly influence stereoselectivity: at low concentrations, L-alcohols were predominantly formed, whereas at higher concentrations, a shift toward D-selectivity was observed, especially for substrate 1c (41 % ee (L) at 0.05 mM; 87 % ee (D) at 5 mM). Furthermore, 1a acted as a competitive inhibitor in the reduction of 1c, effectively altering the enantioselectivity. Additionally, hyperosmotic conditions induced by 0.5 M sorbitol or 0.25 M NaCl increased the yield of L-alcohols, likely by upregulating the expression of the fabG gene, which encodes an NADPH-dependent ketoreductase. These findings provide new insights into the control of stereoselectivity and reaction efficiency in photobiocatalytic reductions using whole-cell cyanobacteria.