Protein-inorganic hybrid nanoflowers were prepared using Cu 2+ , PBS buffer, and a copper ion tolerant L-arabinose isomerase that was derived from Paenibacillus polymyxa (PPAI). The expensive rare sugar L-ribulose or D-tagatose was prepared utilizing these nanoflowers with L-arabinose or D-galactose as the substrate, respectively. The PPAI hybrid nanoflowers showed better enzyme stabilities in both thermal and acidic conditions. Meanwhile, long term batch production was successful showing high stability using these hybrid nanoflowers, which achieved a conversion rate of 61.8% from L-arabinose to L-ribulose.L-Ribose is an important pharmaceutical intermediate for the production of L-form sugar based antivirus drugs including those targeting human immunodeciency virus (HIV), hepatitis B/C virus (HBV/HCV), and human cytomegalovirus (HCMV). 1-3 L-Ribose does not exist in nature and it can only be obtained through chemical synthesis. However, its synthetic route is complicated, which composed of 5-6 steps and the nal yield is low. 1,2 Recently, biological production of L-ribose was established using a two-step reaction: L-arabinose, as the starting raw material, was rstly converted into its ketose isomer L-ribulose by L-arabinose isomerase (namely AI, EC 5.3.1.4), and then isomerized into L-ribose by mannose-6-phosphate isomerase (namely MPI, EC 5.3.1.8). 4,5 This method achieved a conversion rate of 23.6% from L-arabinose to L-ribose and a volumetric productivity of 39.3 g L À1 h À1 . 5 Considering that liquid L-arabinose was easily extracted from corncob bres hydrolysates, this method is economical. On the other hand, AI was widely