title: Biotransformation of colchicinoids into their corresponding 3-O-glucosyl derivatives by selected strains of Bacillus megaterium.
abstract: Natural colchicinoids and their semisynthetic derivatives are important active ingredients for pharmaceutical applications. Thiocolchicoside (3-demethoxy-3-glucosyloxythiocolchicine) is used in several countries as standard therapy for the treatment of diseases of the muscle-skeletal system, due to its potent antiinflammatory and myorelaxant properties. Manufacturing of thiocolchicoside requires a key step, the regioselective demethylation and glucosylation of chemically derivative thiocolchicine. High selectivity and efficiency of this transformation cannot be achieved in a satisfactory way with a chemical approach. In particular, the chemical demethylation, a part from requiring toxic and aggressive reagents, generates a complex mixture of products with no industrial usefulness. We report herein an efficient, direct and green biotransformation of thiocolchicine into thiocolchicoside, performed by a specific strain of Bacillus megaterium. The same process, with minor modifications, can be used to convert the by-product 3-O-demethyl-thiocolchicine into thiocolchicoside. In addition, we describe the B. megaterium strain selection process and the best conditions for this effective double biotransformation. The final product has a pharmaceutical quality, and the process has been industrialised.
authors.affiliation: Indena S.p.A., Via Don Minzoni, 6, Settala, 20090, Milan, Italy, cesare.ponzone@indena.com.
authors.forename: Cesare
authors.initials: C
authors.lastname: Ponzone
authors.forename: Davide
authors.initials: D
authors.lastname: Berlanda
authors.forename: Fabio
authors.initials: F
authors.lastname: Donzelli
authors.forename: Valter
authors.initials: V
authors.lastname: Acquati
authors.forename: Rosalba
authors.initials: R
authors.lastname: Ciulla
authors.forename: Alberto
authors.initials: A
authors.lastname: Negrini
authors.forename: Marco
authors.initials: M
authors.lastname: Rovati
authors.forename: Douglas
authors.initials: D
authors.lastname: Evangelista
authors.forename: Emilio
authors.initials: E
authors.lastname: Fata
authors.forename: Daniele
authors.initials: D
authors.lastname: Ciceri
authors.forename: Federico
authors.initials: F
authors.lastname: Perterlongo
authors.forename: Walter
authors.initials: W
authors.lastname: Cabri
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000627:therapeutic use*; D001410:Bacillus megaterium / Q000378:metabolism; D001711:Biotransformation; D003078:Colchicine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; C014856:thiocholchicine; D003078:Colchicine; C004280:thiocolchicoside