7alpha- and 12alpha-Hydroxysteroid dehydrogenases from Acinetobacter calcoaceticus lwoffii: a new integrated chemo-enzymatic route to ursodeoxycholic acid.
We report the very efficient biotransformation of cholic acid to 7-keto- and 7,12-diketocholic acids with Acinetobacter calcoaceticus lwoffii. The enzymes responsible of the biotransformation (i.e. 7alpha- and 12alpha-hydroxysteroid dehydrogenases) are partially purified and employed in a new chemo-enzymatic synthesis of ursodeoxycholic acid starting from cholic acid. The first step is the 12alpha-HSDH-mediated total oxidation of sodium cholate followed by the Wolf-Kishner reduction of the carbonyl group to chenodeoxycholic acid. This acid is then quantitatively oxidized with 7alpha-HSDH to 7-ketochenodeoxycholic acid, that was chemically reduced to ursodeoxycholic acid (70% overall yield).
Giovannini
Pier Paolo
PP
Dipartimento di Biologia ed Evoluzione, Università di Ferrara, C.so Ercole I d'Este 32, I-44100 Ferrara, Italy.
Grandini
Alessandro
A
Perrone
Daniela
D
Pedrini
Paola
P
Fantin
Giancarlo
G
Fogagnolo
Marco
M
D016954:Acinetobacter calcoaceticus / Q000201:enzymology*; D001711:Biotransformation; D002384:Catalysis; D002478:Cells, Cultured; D002793:Cholic Acids / Q000378:metabolism; D006913:Hydroxysteroid Dehydrogenases / Q000302:isolation & purification / Q000378:metabolism*; D014580:Ursodeoxycholic Acid / Q000378:metabolism*
D002793:Cholic Acids; D014580:Ursodeoxycholic Acid; D006913:Hydroxysteroid Dehydrogenases; C025376:7 alpha-hydroxysteroid dehydrogenase; C019189:12 alpha-hydroxysteroid dehydrogenase