Production of scyllo-Inositol: Conversion of Rice Bran into a Promising Disease-Modifying Therapeutic Agent for Alzheimer's Disease

scyllo-Inositol (SI) is one of the inositol stereoisomers, rare in the nature, and expected as a promising disease-modifying therapeutic agent for Alzheimer's disease. On the other hand, myo-inositol (MI) is another inositol stereoisomer most abundant in nature and thus supplied from agricultural byproducts including rice bran. Bacillus subtilis was genetically modified in its inositol metabolism and phytase secretion, to develope the bioconversion processes to produce SI from rice bran. Phytase, an enzyme that degrades phytate in rice bran into MI, was secreted in a B. subtilis strain with the optimized signal peptide. Another B. subtilis strain was constructed with the constitutive and simultaneous overexpression of IolG and IolW, which are the two inositol dehydrogenases responsible for the conversion, to demonstrate an efficient conversion of MI into SI with a rate up to 10 g/L/48 h. In order to devise further elevation in the conversion efficiency, we attempted to improve the substrate uptake by overexpressing iolT for the major MI transporter. In addition, Escherichia coli pntAB encoding the membrane-bound transhydrogenase was introduced aiming at enhanced supply of NADPH required for the rate-limiting IolW reaction. These additional modifications successfully elevated the conversion efficiency with an improved rate up to almost 30 g/L/48 h. Together with the improved phytase secretion, technological infrastructure for social implementation of SI production from rice bran is on the way.