A bacterial cell factory converting glucose into scyllo-inositol, a therapeutic agent for Alzheimer’s disease
Christophe Michon, Choong‐Min Kang, Sophia Karpenko, Kosei Tanaka, Shu Ishikawa, Ken‐ichi Yoshida
Abstract
Abstract A rare stereoisomer of inositol, scyllo -inositol, is a therapeutic agent that has shown potential efficacy in preventing Alzheimer’s disease. Mycobacterium tuberculosis ino1 encoding myo -inositol-1-phosphate (MI1P) synthase (MI1PS) was introduced into Bacillus subtilis to convert glucose-6-phosphate (G6P) into MI1P. We found that inactivation of pbuE elevated intracellular concentrations of NAD + ·NADH as an essential cofactor of MI1PS and was required to activate MI1PS. MI1P thus produced was dephosphorylated into myo -inositol by an intrinsic inositol monophosphatase, YktC, which was subsequently isomerized into scyllo -inositol via a previously established artificial pathway involving two inositol dehydrogenases, IolG and IolW. In addition, both glcP and glcK were overexpressed to feed more G6P and accelerate scyllo -inositol production. Consequently, a B . subtilis cell factory was demonstrated to produce 2 g L −1 scyllo -inositol from 20 g L −1 glucose. This cell factory provides an inexpensive way to produce scyllo -inositol, which will help us to challenge the growing problem of Alzheimer’s disease in our aging society.