Synthesis of methyl ursodeoxycholate via microbial reduction of methyl 7-ketolithocholate with Eubacterium aerofaciens JCM 7790 grown on two kinds of carbon and hydride sources, glucose and mannitol

Eubacterium aerofaciens JCM 7790, which produces 7β-hydroxysteroid dehydrogenase [7β-HSDH], efficiently catalyzed the reduction of methyl 7-ketolithocholate [Me-7KLCA] to afford methyl ursodeoxycholate [Me-UDCA] in an anaerobic interface bioreactor. For the high accumulation of Me-UDCA, the best supplement of carbon and hydride source to the ABCM medium (glucose content, 0.3 wt.%) was screened because glucose strongly repressed 7β-HSDH production. The supplementation of cellobiose, mannitol, sodium gluconate, and sodium pyruvate was effective to improve the production of Me-UDCA, although many mono- and disaccharides, such as fructose, sucrose, and lactose, strongly repressed 7β-HSDH activity. A phosphate buffer was used as the aqueous phase in the carrier to avoid the lowering of medium pH in the carrier caused by the accumulation of organic acids via fermentation by E. aerofaciens. Thus, the productivity of Me-UDCA was elevated by the combination of glucose and mannitol as carbon and hydride sources and by using a phosphate buffer.