Microbial synthesis of a proton pump inhibitor by enantioselective oxidation of a sulfide into its corresponding sulfoxide by Cunninghamella echinulata MK40

Microbial oxidation of 2-[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methylthiobenzimidazole to a useful proton pump inhibitor, sodium 2-[[4-(3-methoxypropoxy)-3-methylpyridin-2-yl] methylsulfinyl]-1H benzimidazole (Rabeprazole), was examined in over 650 microorganisms. Rabeprazole-forming activity was distributed in molds. The mold with the highest activity was identified as Cunninghamella echinulata. Glucose, when added to the reaction mixture, gave the highest accumulation of Rabeprazole (6.9 mM, 2.5 g l(-)1) with a molar conversion ratio of 92% without the formation of the sulfone form as undesired product and resulted in the exclusive formation of (S) enantiomer (> 99% e.e.).